2,523 results on '"Rauwolfia"'
Search Results
2. Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway.
- Author
-
Wu H, Jiang F, Yuan W, Zhao Y, Liu N, and Miao X
- Subjects
- Animals, Mice, Dextran Sulfate toxicity, Disease Models, Animal, Lipopolysaccharides pharmacology, Polysaccharides metabolism, Alkaloids pharmacology, Colitis metabolism, Colitis, Ulcerative chemically induced, Colitis, Ulcerative drug therapy, Colitis, Ulcerative genetics, Rauwolfia
- Abstract
Background: Ulcerative colitis (UC) is an inflammatory disease of the digestive tract. Rauwolfia polysaccharide (Rau) has therapeutic effects on colitis in mice, but its mechanism of action needs to be further clarified. In the study, we explored the effect of Rau on the UC cell model induced by Lipopolysaccharide (LPS)., Methods: We constructed a UC cell model by stimulating HT-29 cells with LPS. Dextran sodium sulfate (DSS) was used to induce mice to construct an animal model of UC. Subsequently, we performed Rau administration on the UC cell model. Then, the therapeutic effect of Rau on UC cell model and was validated through methods such as Cell Counting Kit-8 (CCK8), Muse, Quantitative real‑time polymerase chain reaction (RT-qPCR), Western blotting, and Enzyme-linked immunosorbent assay (ELISA)., Results: The results showed that Rau can promote the proliferation and inhibit the apoptosis of the HT-29 cells-induced by LPS. Moreover, we observed that Rau can inhibit the expression of NOS2/JAK2/STAT3 in LPS-induced HT-29 cells. To further explore the role of NOS2 in UC progression, we used siRNA technology to knock down NOS2 and search for its mechanism in UC. The results illustrated that NOS2 knockdown can promote proliferation and inhibit the apoptosis of LPS-induced HT-29 cells by JAK2/STAT3 pathway. In addition, in vitro and in vivo experiments, we observed that the activation of the JAK2/STAT3 pathway can inhibit the effect of Rau on DSS-induced UC model., Conclusion: In short, Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway. This study provides a theoretical clue for the treatment of UC by Rau., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
- Full Text
- View/download PDF
3. Alkaloids and Lignans from the Aerial Parts of Rauvolfia tetraphylla Inhibit NO Production in LPS-activated RAW 264.7 Cells.
- Author
-
Tung NKT, Dung DT, Kiem PV, Hang DTT, Nhiem NX, The NV, Seo Y, Kang JS, and Tai BH
- Subjects
- Animals, Mice, RAW 264.7 Cells, Lipopolysaccharides pharmacology, Nitric Oxide, Magnetic Resonance Spectroscopy, Plant Components, Aerial chemistry, Yohimbine, Molecular Structure, Lignans chemistry, Rauwolfia, Alkaloids analysis, Anisoles, Naphthalenes
- Abstract
Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18β-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), N
b -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-β-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-β-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-β-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56 μM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66 μM. The other isolates were inactive with IC50 values over 100 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)- Published
- 2024
- Full Text
- View/download PDF
4. Biotechnological interventions and indole alkaloid production in Rauvolfia serpentina
- Author
-
Abhijit Dey, Debleena Roy, Vikas Moreshwar Mohture, Mimosa Ghorai, Md. Habibur Rahman, Uttpal Anand, Saikat Dewanjee, null Radha, Manoj Kumar, Dorairaj Arvind Prasanth, Niraj Kumar Jha, Saurabh Kumar Jha, Mahipal S. Shekhawat, and Devendra Kumar Pandey
- Subjects
General Medicine ,Plant Roots ,Secologanin Tryptamine Alkaloids ,Applied Microbiology and Biotechnology ,Rauwolfia ,Indole Alkaloids ,Biotechnology - Abstract
Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae), commonly known as Sarpagandha or Indian snakeroot, has long been used in the traditional treatment of snakebites, hypertension, and mental illness. The plant is known to produce an array of indole alkaloids such as reserpine, ajmaline, amalicine, etc. which show immense pharmacological and biomedical significance. However, owing to its poor seed viability, lesser germination rate and overexploitation for several decades for its commercially important bioactive constituents, the plant has become endangered in its natural habitat. The present review comprehensively encompasses the various biotechnological tools employed in this endangered Ayurvedic plant for its in vitro propagation, role of plant growth regulators and additives in direct and indirect regeneration, somatic embryogenesis and synthetic seed production, secondary metabolite production in vitro, and assessment of clonal fidelity using molecular markers and genetic transformation. In addition, elicitation and other methods of optimization of its indole-alkaloids are also described herewith. KEY POINTS: • Latest literature on in vitro propagation of Rauvolfia serpentina • Biotechnological production and optimization of indole alkaloids • Clonal fidelity and transgenic studies in R. serpentina.
- Published
- 2022
5. No Free Lunch With Herbal Preparations: Lessons From a Case of Parkinsonism and Depression Due to Herbal Medicine Containing Reserpine
- Author
-
Michel Rijntjes and Philipp T. Meyer
- Subjects
Parkinson ,depression ,reserpine ,VMAT ,ayurvedic ,Rauwolfia ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The increasing use of herbal medicines calls for a heightened awareness of their potential side-effects. This especially pertains to western countries, where patients tend to use herbal medicine as self-medication, often alongside regular prescriptions, and physicians have less experience with their application. Here we report a case in which Parkinsonism, depression, and an atypical finding detected by dopamine transporter single-photon emission computed tomography were all belatedly recognized as side-effects of herbal medicine. This only occurred because one of its active ingredients, reserpine, has been extensively studied. For most other herbal medicines, however, knowledge about side-effects remains scarce or unavailable. Therefore, we suggest that physicians, when taking a medication history, should actively ask for the use of any herbal preparations.
- Published
- 2019
- Full Text
- View/download PDF
6. Green synthesis of MnO 2 -embedded Rauvolfia tetraphylla leaves (MnO 2 @RTL) for crystal violet dye removal and as an antibacterial agent.
- Author
-
Samal PP, Swain J, Qaiyum MA, Ghosh A, Mandal D, Dey B, and Dey S
- Subjects
- Wastewater, Gentian Violet, Anti-Bacterial Agents pharmacology, Manganese Compounds, Reproducibility of Results, Oxides, Thermodynamics, Adsorption, Hydrogen-Ion Concentration, Kinetics, Spectroscopy, Fourier Transform Infrared, Rauwolfia, Water Pollutants, Chemical chemistry
- Abstract
The application of green synthesized nanocomposites for the prevention of environmental pollution is increasing nowadays. Here, a green composite has been synthesized by embedding MnO
2 on Rauvolfia tetraphylla leaves using its leaf extract hereinafter termed as MnO2 @RTL, and demonstrated for crystal violet (CV) dye removal from simulated and real wastewater. The surface properties of the material were determined by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), and Brunauer-Emmet-Teller (BET) surface area, pHZPC , and zeta potential. The material exhibits a remarkable adsorption capacity of 61.162 mg/g at 328 K and pH 7. The adsorption was best fitted with Pseudo-second-order kinetic (R2 = 0.998) and a combination of Langmuir and Freundlich isotherm model (R2 = 0.994-0.999). The thermodynamic study revealed spontaneous (ΔG values = - 2.988 to - 4.978 kJ/mol) and endothermic (ΔH values = 6.830 to 11.018 kJ/mol) adsorption. After adsorption, 80% regeneration occurred with 50% methanol, and recycled up to five times. Advantageously, the material was able to remove CV dye in the presence of coexistent ions and from industrial wastewater, confirming field applicability. The adsorption capacity of the material is superior to previously reported materials. The standard deviation and relative standard deviations have been evaluated to be 0.000422-0.000667 and 0.473-0.749%, which suggests the reliability of the experiments. The exhausted material, after recycling, was pyrolyzed to overcome the disposal problem. It was established as a secondary adsorbent with 73% efficiency which makes the material win-win. The material showed antibacterial properties with Staphylococcus aureus bacteria with a zone of inhibition 5 mm., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
- Full Text
- View/download PDF
7. No Free Lunch With Herbal Preparations: Lessons From a Case of Parkinsonism and Depression Due to Herbal Medicine Containing Reserpine.
- Author
-
Rijntjes, Michel and Meyer, Philipp T.
- Subjects
HERBAL medicine ,SINGLE-photon emission computed tomography ,RESERPINE ,PARKINSONIAN disorders - Abstract
The increasing use of herbal medicines calls for a heightened awareness of their potential side-effects. This especially pertains to western countries, where patients tend to use herbal medicine as self-medication, often alongside regular prescriptions, and physicians have less experience with their application. Here we report a case in which Parkinsonism, depression, and an atypical finding detected by dopamine transporter single-photon emission computed tomography were all belatedly recognized as side-effects of herbal medicine. This only occurred because one of its active ingredients, reserpine, has been extensively studied. For most other herbal medicines, however, knowledge about side-effects remains scarce or unavailable. Therefore, we suggest that physicians, when taking a medication history, should actively ask for the use of any herbal preparations. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
8. Anti-fouling potential and in-silico analysis of carotenoid and fatty acids from Rauvolfia tetraphylla L.
- Author
-
Ravi P, Kumaresan S, Danaraj J, Uthirakrishnan U, Pandian S, Sivaramakrishnan R, Prakasam SB, and Pugazhendhi A
- Subjects
- Fatty Acids, Plant Extracts pharmacology, Plant Extracts chemistry, Molecular Docking Simulation, Palmitic Acid, Oleic Acid, Carotenoids, Biofouling prevention & control, Rauwolfia
- Abstract
Study investigated the antifouling potential ofRauvolfia tetraphyllaL. fruit, leaf and stem extracts against the marine fouling organisms throughin-vitroand in-silicoapproach. Methanolic crude extract of R. tetraphylla L.leaf exhibited maximum antibacterial potential against six fouling organisms isolated from Parangipettai coast and was further taken up for column fractionation. Twenty-four fractions were obtained, among which five fractions showed inhibitory efficiency against microfoulers of Bacillus megaterium. The active compounds present in the bioactive fraction were identified by FTIR, GC-MS and NMR (13C; 1H). The bioactive compounds that exhibited maximum antifouling activity were identified as Lycopersene (80%), Hexadecanoic acid; 1, 2-Benzenedicarboxylic acid, dioctyl ester; Heptadecene - (8) - carbonic acid - (1) and Oleic acid. Molecular docking studies of the potent anti-fouling compounds Lycopersene, Hexadecanoic acid, 1, 2-Benzenedicarboxylic acid, dioctyl ester and Oleic acid showed the binding energy of 6.6, - 3.8, -5.3 and -5.9 (Kcal/mol) and hence these compounds will act as a potential biocide to control the aquatic foulers. Moreover, further studies need to carry out in terms of toxicity, field assessment and clinical trial in order to take these biocides for a patent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
9. Virus-induced gene silencing in Rauwolfia species.
- Author
-
Corbin, Cyrielle, Lafontaine, Florent, Sepúlveda, Liuda, Carqueijeiro, Ines, Courtois, Martine, Lanoue, Arnaud, Dugé de Bernonville, Thomas, Besseau, Sébastien, Glévarec, Gaëlle, Papon, Nicolas, Atehortúa, Lucia, Giglioli-Guivarc'h, Nathalie, Clastre, Marc, St-Pierre, Benoit, Oudin, Audrey, and Courdavault, Vincent
- Subjects
- *
RAUVOLFIA , *PLANT gene silencing , *TOBACCO rattle virus , *PHYTOENE desaturase , *MEDICINAL plants - Abstract
Elucidation of the monoterpene indole alkaloid biosynthesis has recently progressed in Apocynaceae through the concomitant development of transcriptomic analyses and reverse genetic approaches performed by virus-induced gene silencing (VIGS). While most of these tools have been primarily adapted for the Madagascar periwinkle ( Catharanthus roseus), the VIGS procedure has scarcely been used on other Apocynaceae species. For instance, Rauwolfia sp. constitutes a unique source of specific and valuable monoterpene indole alkaloids such as the hypertensive reserpine but are also well recognized models for studying alkaloid metabolism, and as such would benefit from an efficient VIGS procedure. By taking advantage of a recent modification in the inoculation method of the Tobacco rattle virus vectors via particle bombardment, we demonstrated that the biolistic-mediated VIGS approach can be readily used to silence genes in both Rauwolfia tetraphylla and Rauwolfia serpentina. After establishing the bombardment conditions minimizing injuries to the transformed plantlets, gene downregulation efficiency was evaluated at approximately a 70% expression decrease in both species by silencing the phytoene desaturase encoding gene. Such a gene silencing approach will thus constitute a critical tool to identify and characterize genes involved in alkaloid biosynthesis in both of these prominent Rauwolfia species. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
10. Developments in biotechnological tools and techniques for production of reserpine.
- Author
-
Swain H, Gantait S, and Mandal N
- Subjects
- Humans, Reserpine metabolism, Biotechnology methods, Bioreactors, Plant Roots metabolism, Rauwolfia, Plants, Medicinal, Alkaloids metabolism
- Abstract
In the quest for novel medications, researchers have kept on studying nature to unearth beneficial plant species with medicinal qualities that may cure various diseases and disorders. These medicinal plants produce different bioactive secondary metabolites with immense therapeutic importance. One such valuable secondary metabolite, reserpine (C
33 H40 N2 O9 ), has been used for centuries to cure various ailments like hypertension, cardiovascular diseases, neurological diseases, breast cancer, and human promyelocytic leukaemia. Rauvolfia spp. (family Apocynaceae) is an essential reservoir of this reserpine. The current review thoroughly covers different non-conventional or in vitro-mediated biotechnological methods adopted for pilot-scale as well as large-scale production of reserpine from Rauvolfia spp., including techniques like multiple shoot culture, callus culture, cell suspension culture, precursor feeding, elicitation, synthetic seed production, scale-up via bioreactor, and hairy root culture. This review further analyses the unexplored and cutting-edge biotechnological tools and techniques to alleviate reserpine production. KEY POINTS: • Reserpine, a vital indole alkaloid from Rauvolfia spp., has been used for centuries to cure several ailments. • Overview of biosynthetic pathways and biotechnological applications for enhanced production of reserpine. • Probes the research gaps and proposes novel alternative techniques to meet the pharmaceutical industry's need for reserpine while reducing the over-exploitation of natural resources., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
- Full Text
- View/download PDF
11. Chemical composition, antioxidant, and enzyme inhibitory properties of Rauwolfia vomitoria extract.
- Author
-
Adebayo AA, Ademosun AO, and Oboh G
- Subjects
- Male, Humans, Antioxidants pharmacology, Arginase, Antihypertensive Agents, Phenols pharmacology, Plant Extracts pharmacology, Erectile Dysfunction, Rauwolfia
- Abstract
Objectives: Rauwolfia vomitoria is one ethno-botanicals in Nigeria used by traditional health practitioners in managing several human diseases. However, necessary information regarding its effect on enzymes implicated in the development and progression of erectile dysfunction is missing in the literature. Thus, this study investigated the antioxidant property and impact of Rauwolfia vomitoria extract on erectile dysfunction-related enzymes in vitro., Methods: High performance liquid chromatography was used to identify and quantify Rauwolfia vomitoria 's phenolic components. Then, utilizing common antioxidant assays, the extract's antioxidant properties were evaluated and finally the effect of the extract on some enzymes (AChE, arginase and ACE) implicated in erectile dysfunction was investigated in vitro ., Results: The results showed that the extract inhibited AChE (IC
50 =388.72 μg/mL), arginase (IC50 =40.06 μg/mL) and ACE (IC50 =108.64 μg/mL) activities. In addition, phenolic rich extract of Rauvolfia vomitoria scavenged radicals and chelated Fe2+ in concentration dependent manner. Furthermore, rutin, chlorogenic acid, gallic acid, and kaempferol were found in large quantities by HPLC analysis., Conclusions: Therefore, one of the potential reasons driving Rauwolfia vomitoria 's use in folk medicine for the treatment of erectile dysfunction could be its antioxidant and inhibitory activities on several enzymes linked to erectile dysfunction in vitro ., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2023
- Full Text
- View/download PDF
12. Murine’s amygdala microstructure and elevated plus maze activities following R. vomitoria root bark and G. latifolium leaf extracts administration
- Author
-
Idongesit S Nduohosewo and Moses B. Ekong
- Subjects
Male ,medicine.medical_specialty ,Elevated plus maze ,Body weight ,Amygdala ,Rauwolfia ,Mice ,03 medical and health sciences ,symbols.namesake ,Internal medicine ,medicine ,Animals ,Maze Learning ,030304 developmental biology ,0303 health sciences ,Glial fibrillary acidic protein ,biology ,Plant Extracts ,Rauvolfia vomitoria ,General Medicine ,biology.organism_classification ,Apocynaceae ,Plant Leaves ,Endocrinology ,medicine.anatomical_structure ,030301 anatomy & morphology ,visual_art ,Plant Bark ,biology.protein ,visual_art.visual_art_medium ,Nissl body ,symbols ,Bark ,Anatomy ,Pyknosis - Abstract
R. vomitoria (RV), a plant used locally in the management of psychotic disorders, adversely affects the brain functionally and structurally. Such adverse reports, as well as the potential of G. latifolium (GL) to mitigate same warranted this investigation on the combined actions of RV and GL on the amygdala. Twenty-four male CD-1 mice weighing 22-27 g were divided into four groups (n = 6): Control (20 ml/kg body weight, b.w., distilled water); RV (200 mg/kg b.w.), GL (200 mg/kg b.w.), and RV (200 mg/kg b.w.) and GL (200 mg/kg b.w.) combination orally, and for 14 days. On day 15, the elevated-plus maze test was carried out and the animals sacrificed, and processed for histological and immunohistochemical studies. Neurobehavioural results showed significant decrease (p[Formula: see text] 0.001) in stretch-attend posture, time spent in closed arms, grooming frequency, protected head-dip, as well as significantly (p [Formula: see text] 0.01) increased time spent in the open arms and unprotected head-dips of the RV group. The combined RV and GL groups showed no such differences in these parameters. Histologically, the amygdala showed hypertrophied cells, with pyknotic and karyorrhectic nuclei, and reduced expression of Nissl substance in the RV group, while the combined RV and GL group showed less degenerative features. Glial fibrillary acidic protein expression (GFAP) was increased in the RV group, while the combined RV and GL group showed reduced expression. In conclusion, RV root bark extract has adverse effects on the microstructure of murines' amygdala and their behaviour, which may be ameliorated by GL.
- Published
- 2020
13. A Serum Metabolomics Study Based on LC-MS: Chemosensitization Effects of Rauvolfia Vomitoria Afzel. Combined with 5-Fluorouracil on Colorectal Cancer Mice
- Author
-
Zhi-Fan Wang, Wen-Ru Kong, Ning Wang, Yu-Lin You, Jian-Feng Wang, and Shu-Qi Wang
- Subjects
History ,Polymers and Plastics ,Clinical Biochemistry ,Fatty Acids ,Pharmaceutical Science ,Lipids ,Rauwolfia ,Industrial and Manufacturing Engineering ,Analytical Chemistry ,Mice ,Tandem Mass Spectrometry ,Cell Line, Tumor ,Drug Discovery ,Animals ,Fluorouracil ,Business and International Management ,Colorectal Neoplasms ,Spectroscopy ,Chromatography, Liquid - Abstract
Colorectal cancer (CRC) is one of the malignant tumors with high incidence, and is mainly treated by chemotherapy at present. However, during CRC treatment, long-term use of traditional chemotherapeutic drugs will reduce the sensitivity of chemotherapy. Our previous studies have shown that Rauvolfia vomitoria total alkaloids (RVA) played an important role in 5-fluorouracil (5-FU) chemosensitization in CRC therapy, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, LC-MS based metabolomics was employed to explore the mechanism of 5-FU chemosensitization in CRC induced by the combination of RVA and conventional chemotherapeutic with 5-FU. The results showed that the final tumor weight of the high-dose combined group was significantly different from that of the 5-FU alone group. To evaluate the chemosensitization effects of RVA, serum samples collected from six groups (six mice in each group) with different administration methods were analyzed by HPLC-Q-Exactive Orbitrap/MS. After multivariate statistical analysis and metabolites identification, 25 different metabolites were identified between the 5-FU treatment group and combined high-dose treatment group, among which lipid and fatty acid metabolism pathways were mostly affected. These results suggest that RVA may sensitize traditional chemotherapeutic drug 5-FU and exert anti-tumor activity through influencing lipid metabolism and cell energy metabolism. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine in treating colorectal cancer.
- Published
- 2022
14. Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress
- Author
-
Guifang Huang, Xiao He, Zesheng Xue, Yiming Long, Jiakuan Liu, Jinming Cai, Pengfei Tang, Bangmin Han, Bing Shen, Ruimin Huang, and Jun Yan
- Subjects
Male ,Complementary and alternative medicine ,Autophagy ,Prostatic Hyperplasia ,Animals ,Humans ,Apoptosis ,Endoplasmic Reticulum Stress ,Rauwolfia ,Rats - Abstract
Background The current drug treatments for benign prostatic hyperplasia (BPH) have negative side effects. Therefore, it is important to find effective alternative therapies with significantly fewer side effects. Our previous study revealed that Rauwolfia vomitoria (RWF) root bark extract reversed BPH development in a rat model. However, the molecular mechanism of its inhibitory effects on BPH remains largely unknown. Methods BPH-1 and WPMY-1 cell lines derived from BPH epithelial and prostatic stromal compartments were selected to investigate how RWF extract inhibits BPH in vitro by MTT and flow cytometry assays. Microarray, quantitative real-time PCR, immunoblotting, and GFP-LC3 immunofluorescence assays were performed to evaluate the effects of RWF extract on endoplasmic reticulum stress (ER stress) and autophagic apoptosis pathways in two cell lines. A human BPH ex vivo explant assay was also employed for validation. Results RWF extract treatment decreased cell viability and induced apoptotic cell death in both BPH-1 and WPMY-1 cells in a concentration-dependent manner with the increase of pro-apoptotic PCDC4 protein. RWF extract induced autophagy by enhancing the levels of autophagic genes (ULK2 and SQSTM1/p62) and the LC3II:LC3I ratio, with the increase of GFP-LC3 puncta. Moreover, RWF extract activated PERK- and ATF6-associated ER stress pathways by inducing the transcriptional levels of EIF2AK3/PERK, DDIT3/CHOP and ATF6, accompanied by the reduction of BiP protein level, but not its mRNA level. Another ER stress pathway was not induced by RWF extract, as manifested by the lack of XBP1 splicing. Pharmacological inhibition of autophagy by 3-methyladenine abrogated apoptosis but not ER stress; while inhibition of ER stress by 4-phenylbutyrate alleviated the induction of autophagy and apoptosis. In addition, pretreatments with either 3-methyladenine or 4-phenylbutyrate suppressed RWF extract-induced cytotoxicity. Notably, the inductions of PERK- and ATF6-related stress pathways and autophagic apoptosis were confirmed in a human BPH ex vivo explant. Conclusions Our data have demonstrated that RWF extract significantly suppressed the viabilities of BPH epithelial cells and BPH myofibroblasts by inducing apoptosis via upregulating ER stress and autophagy. These data indicate that RWF extract is a potential novel alternative therapeutic approach for BPH.
- Published
- 2021
15. Indian
- Author
-
Prakash N, Tandon
- Subjects
Special Opinion Paper ,Humans ,History, 20th Century ,Antihypertensive Agents ,Rauwolfia ,Nobel Prize - Published
- 2021
16. Genus Rauvolfia: A review of its ethnopharmacology, phytochemistry, quality control/quality assurance, pharmacological activities and clinical evidence
- Author
-
Sunil Kumar, Diksha Kumari, and Bikarma Singh
- Subjects
Quality Control ,Pharmacology ,Plants, Medicinal ,Cardiovascular Diseases ,Plant Extracts ,Ethnopharmacology ,Phytochemicals ,Drug Discovery ,Humans ,Antihypertensive Agents ,Rauwolfia ,Indole Alkaloids ,Phytotherapy - Abstract
The plants are from the genus Rauvolfia Plum. ex L. (Apocynaceae), which is represented by 74 species with many synonyms, and distributed worldwide, especially in the Asian, and African continents. Traditionally, some of them are used for the treatment of various disorders related to the central nervous system (CNS), cardiovascular diseases (CVD), and as an antidote due to the presence of monoterpene indole alkaloids (MIAs) such as ajmaline (144), ajmalicine (164) serpentine (182), yohimbine (190) and reserpine (214).The present review provides comprehensive summarization and critical analysis of the traditional to modern applications of Rauvolfia species, and the major focus was to include traditional uses, phytochemistry, quality control, pharmacological properties, as well as clinical evidence that may be useful in the drug discovery process.Information related to traditional uses, chemical constituents, separation techniques/analytical methods, and pharmacological properties of the genus Rauvolfia were obtained using electronic databases such as Web of Science, Scopus, SciFinder, PubMed, PubChem, ChemSpider, and Google Scholar between the years 1949-2021. The scientific name of the species and its synonyms were checked with the information of The Plant List.A total of seventeen Rauvolfia species have been traditionally explored for various therapeutic applications, out of which the roots of R. serpentina and R. vomitoria are used most commonly for the treatment of many diseases. About 287 alkaloids, seven terpenoids, nine flavonoids, and four phenolic acids have been reported in different parts of the forty-three species. Quality control (QC)/quality assurance (QA) of extracts/herbal formulations of Rauvolfia species was analyzed by qualitative and quantitative methods based on the major MIAs such as compounds 144, 164, 182, 190, and 214 using HPTLC, HPLC, and HPLC-MS. The various extracts of different plant parts of thirteen Rauvolfia species are explored for their pharmacological properties such as antimicrobial, antioxidant, antiprotozoal, antitrypanosomal, antipsychotic, cardioprotective, cholinesterase inhibitory, and hepatoprotective. Of which, clinical trials of herbal formulations/extracts of R. serpentina and MIAs have been reported for CVD, CNS, antihypertensive therapy, antidiabetic effects, and psoriasis therapy, while the extracts and phytoconstituents of remaining Rauvolfia species are predominantly significant, owning them to be additional attention for further investigation under clinical trials and QC/QA.The present communication has provided a comprehensive, systematic, and critically analyzed vision into the traditional uses, phytochemistry, and modern therapeutic applications of the genus Rauvolfia are validated by scientific evidence. In addition, different plant parts from this genus, especially raw and finished herbal products of the roots of R. serpentina have been demonstrated for the QC/QA.
- Published
- 2022
17. Antioxidant and haematinic effects of methanolic and aqueous methanolic roots extracts of Rauwolfia serpentina Benth in type 2 diabetic mice
- Author
-
Muhammad Bilal, Azmi, Shamim, A Qureshi, Shakil, Ahmed, Saleha, Sultana, Auwais Ahmed, Khan, and Hina Akram, Mudassir
- Subjects
Erythrocyte Indices ,Plant Extracts ,Superoxide Dismutase ,Catalase ,Plant Roots ,Antioxidants ,Rauwolfia ,Diabetes Mellitus, Experimental ,Hemoglobins ,Leukocyte Count ,Mice ,Diabetes Mellitus, Type 2 ,Hematocrit ,Erythrocyte Count ,Hematinics ,Animals - Abstract
Present investigation was carried out to evaluate the antioxidant and haematinic effects of methanolic (MREt) and aqueous methanolic (AqMREt) root extracts of R. serpentina in mice model of type 2 diabetes (T2D). Experimental mice were divided into nine groups (six per group) as: fructose-induced (T2D) diabetic group (distilled water 1ml/kg), negative control (0.05% DMSO 1ml/kg), positive control (pioglitazone 15mg/kg) and six test groups (MREt 10, 3060mg/kgAqMREt 50, 100150mg/kg). Whereas tenth group was served as normal control (1ml/kg distilled water). All test doses of MREtAqMREt significantly (p0.05) decreases the percent inhibition of catalase (CAT) and superoxide dismutase (SOD) when compared with diabetic controls. Treatment with both extracts also improved the total hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) counts, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) in test groups. Fourier transform infrared (FTIR) spectral analysis revealed the presence of phenols moiety in both extracts. Findings suggested that AqMREt possesses more antioxidant and haematinic potential while the MREt of R. serpentina moderately possesses the same activities, which might be due to the high content of phenols present in AqMREt.
- Published
- 2021
18. Therapeutic role of Rauwolfia serpentina in minimizing the risk of glycosylation and associated biomarkers in experimentally induced type 1 diabetic mice
- Author
-
Muhammad Bilal, Azmi, Shamim Akhtar, Qureshi, Syed Danish, Haseen Ahmed, Auwais Ahmed, Khan, Muhammad, Ahsan, Hina Akram, Mudassir, Fauzia, Imtiaz, and Sumera, Rais
- Subjects
Male ,Mice ,Diabetes Mellitus, Type 1 ,Glycosylation ,Plant Extracts ,Alloxan ,Animals ,Biomarkers ,Rauwolfia ,Diabetes Mellitus, Experimental - Abstract
Present work investigates the effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 diabetic mice. Mice were divided into normal, diabetic, negative and positive controls (I-IV) and three test (HyMREt doses) groups (V-VII - 50, 100,150mg/kg). Allocated treatment of each group was given orally for 14 days in overnight fasted state. Percent change in fasting blood glucose (FBG), body weights, body tissue weights, hepatic glycogen, total lipids, glycosylated hemoglobin (HbA
- Published
- 2021
19. Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure
- Author
-
Mahesh Ayyavu, Ashok Kumar, Kannan Narayanan Dhiraviam, and Manjula Devi Ramamoorthy
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Reserpine ,Apoptosis ,Pharmacology ,030226 pharmacology & pharmacy ,Rauwolfia ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Annexin ,medicine ,Humans ,MTT assay ,Inner mitochondrial membrane ,Membrane Potential, Mitochondrial ,chemistry.chemical_classification ,Reactive oxygen species ,Acridine orange ,Prostatic Neoplasms ,Cell Cycle Checkpoints ,Cell cycle ,Antineoplastic Agents, Phytogenic ,030104 developmental biology ,chemistry ,PC-3 Cells ,Molecular Medicine ,medicine.drug - Abstract
Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.
- Published
- 2019
20. Antimicrobial and cytotoxic activities of indole alkaloids and other constituents from the stem barks of
- Author
-
Andre Nehemie, Bitombo, Auguste Abouem A, Zintchem, Alex de Théodore, Atchadé, Esther Del Florence, Moni Ndedi, Afsar, Khan, Dominique Serge, Ngono Bikobo, Dieudonné Emmanuel, Pegnyemb, and Christian G, Bochet
- Subjects
Apocynaceae ,Anti-Infective Agents ,Molecular Structure ,Rauwolfia ,Anti-Bacterial Agents ,Indole Alkaloids - Abstract
Twenty indole alkaloids, among which two undescribed ones named rauvolfianoids A (
- Published
- 2021
21. Pectic polysaccharides derived from Hainan Rauwolfia ameliorate NLR family pyrin domain-containing 3-mediated colonic epithelial cell pyroptosis in ulcerative colitis.
- Author
-
Yuan W, Tian Y, Lin C, Wang Y, Liu Z, Zhao Y, Chen F, and Miao X
- Subjects
- Animals, Mice, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Pectins adverse effects, Pyroptosis, Pyrin Domain, Epithelial Cells metabolism, Disease Models, Animal, Mice, Inbred C57BL, Colitis, Ulcerative chemically induced, Colitis, Ulcerative drug therapy, Rauwolfia metabolism, Colitis chemically induced, MicroRNAs
- Abstract
Pectic polysaccharides (PPs) could exert functions on ulcerative colitis (UC), which is classified as a nonspecific inflammatory disorder. This study investigated the molecular mechanism of PPs derived from Rauwolfia in UC. First, the dextran sodium sulfate (DSS)-induced mouse colitis models and lipopolysaccharide (LPS)-treated colonic epithelial cell (YAMC) models were established and treated with PP. Subsequently, the effects of PPs on mucosal damages in DSS mice were detected, and the levels of inflammatory cytokines, pyroptosis-related factors, oxidative stress-related markers, and the tight junction-related proteins in the tissues or cells were examined, and the results suggested that PPs ameliorated colonic mucosal damages and cell pyroptosis in DSS mice, and limited colonic epithelial cell pyroptosis in in vitro UC models. Subsequently, the binding relations of retinol-binding protein 4 (RBP4) to miR-124-3p and NLR pyrin domain-containing 3 (NLRP3) were analyzed. miR-124-3p targeted RBP4 and reduced the binding of RBP4 to NLRP3, thus inhibiting NLRP3-mediated pyroptosis. Finally, functional rescue experiments revealed that miR-124-3p suppression or RBP4 overexpression promoted colonic epithelial cell pyroptosis. Collectively, Rauwolfia-derived PPs limited miR-124-3p and targeted RBP4 and reduced the binding potency of RBP4 to NLRP3 to inhibit NLRP3-mediated pyroptosis, resulting in the alleviation of colonic epithelial cell pyroptosis and mucosal damages in UC.
- Published
- 2023
- Full Text
- View/download PDF
22. Hairy root biotechnology of Rauwolfia serpentina: a potent approach for the production of pharmaceutically important terpenoid indole alkaloids.
- Author
-
Mehrotra, Shakti, Goel, Manoj, Srivastava, Vikas, and Rahman, Laiq
- Subjects
RAUVOLFIA serpentina ,RHIZOBIUM rhizogenes ,INDOLE alkaloids ,BIOREACTORS ,TISSUE culture ,THERAPEUTIC use of alkaloids - Abstract
Hairy root cultures of Rauwolfia serpentina induced by Agrobacterium rhizogenes have been investigated extensively for the production of terpenoid indole alkaloids. Various biotechnological developments, such as scaling up in bioreactors, pathway engineering etc., have been explored to improve their metabolite production potential. These hairy roots are competent for regenerating into complete plants and show survival and unaltered biosynthetic potential during storage at low temperature. This review provides a comprehensive account of the hairy root cultures of R. serpentina, their biosynthetic potential and various biotechnological methods used to explore the production of pharmaceutically important terpenoid indole alkaloids. The review also indicates how biotechnological endeavors might improve the future progress of research for production of alkaloids using Rauwolfia hairy roots. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
23. A serum metabolomics study based on LC-MS: Chemosensitization effects of Rauvolfia vomitoria Afzel. combined with 5- fluorouracil on colorectal cancer mice.
- Author
-
Wang ZF, Kong WR, Wang N, You YL, Wang JF, and Wang SQ
- Subjects
- Animals, Cell Line, Tumor, Chromatography, Liquid, Fatty Acids, Fluorouracil pharmacology, Fluorouracil therapeutic use, Lipids, Mice, Tandem Mass Spectrometry, Colorectal Neoplasms drug therapy, Rauwolfia
- Abstract
Colorectal cancer (CRC) is one of the malignant tumors with high incidence, and is mainly treated by chemotherapy at present. However, during CRC treatment, long-term use of traditional chemotherapeutic drugs will reduce the sensitivity of chemotherapy. Our previous studies have shown that Rauvolfia vomitoria total alkaloids (RVA) played an important role in 5-fluorouracil (5-FU) chemosensitization in CRC therapy, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, LC-MS based metabolomics was employed to explore the mechanism of 5-FU chemosensitization in CRC induced by the combination of RVA and conventional chemotherapeutic with 5-FU. The results showed that the final tumor weight of the high-dose combined group was significantly different from that of the 5-FU alone group. To evaluate the chemosensitization effects of RVA, serum samples collected from six groups (six mice in each group) with different administration methods were analyzed by HPLC-Q-Exactive Orbitrap/MS. After multivariate statistical analysis and metabolites identification, 25 different metabolites were identified between the 5-FU treatment group and combined high-dose treatment group, among which lipid and fatty acid metabolism pathways were mostly affected. These results suggest that RVA may sensitize traditional chemotherapeutic drug 5-FU and exert anti-tumor activity through influencing lipid metabolism and cell energy metabolism. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine in treating colorectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
24. Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC-MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats
- Author
-
Meng-Yu Li, Li-Yuan Zhang, Yue-Wu Xie, Shu-Qi Wang, Yu-Lin You, Fei-Fei Li, and Ning Wang
- Subjects
Male ,Administration, Oral ,Filtration and Separation ,Pharmacology ,01 natural sciences ,Rauwolfia ,Streptozocin ,Analytical Chemistry ,Diabetes Mellitus, Experimental ,Indole Alkaloids ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Oral administration ,Diabetes mellitus ,medicine ,Animals ,Hypoglycemic Agents ,Ajmalicine ,Plants, Medicinal ,biology ,Molecular Structure ,business.industry ,010401 analytical chemistry ,Rauvolfia vomitoria ,Reserpine ,biology.organism_classification ,medicine.disease ,0104 chemical sciences ,Yohimbine ,Rats ,Ajmaline ,chemistry ,Diabetes Mellitus, Type 2 ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.
- Published
- 2020
25. Acetylcholinesterase inhibitory activity of extract and fractions from the root of
- Author
-
Suciati, Debora, Poerwantoro, Aty, Widyawaruyanti, and Kornkanok, Ingkaninan
- Subjects
1-Butanol ,Alkaloids ,Plant Extracts ,Butyrylcholinesterase ,Phytochemicals ,Acetylcholinesterase ,Cholinesterase Inhibitors ,Rauwolfia - Abstract
Alzheimer's disease (AD) is a degenerative brain disease characterized by confusion, behavior changes, decline in memory and cognitive skills. One of the strategies in the treatment of AD is to use acetylcholinesterase (AChE) inhibitors. The current study aims to determine the AChE inhibitory activities of the extract and fractions of the root ofExtraction was carried out by maceration method using ethanol, followed by liquid-liquid partition usingThe ethanolic extract ofThe ethanolic extract, as well as fractions of
- Published
- 2020
26. Cytotoxic Yohimbine‐Type Alkaloids from the Leaves of Rauvolfia vomitoria
- Author
-
Xinxin Zhang, Guanqun Zhan, Zengjun Guo, Xingbin Wang, Fuxin Zhang, and Rongkun Miao
- Subjects
Stereochemistry ,Monoterpene ,Bioengineering ,01 natural sciences ,Biochemistry ,Rauwolfia ,Indole Alkaloids ,Cell Line, Tumor ,medicine ,Humans ,Cytotoxic T cell ,Carbon-13 Magnetic Resonance Spectroscopy ,Cytotoxicity ,Molecular Biology ,Indole test ,biology ,Apocynaceae ,010405 organic chemistry ,Chemistry ,Rauvolfia vomitoria ,Yohimbine ,General Chemistry ,General Medicine ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,0104 chemical sciences ,Plant Leaves ,010404 medicinal & biomolecular chemistry ,Cell culture ,Molecular Medicine ,medicine.drug - Abstract
Two new yohimbine-type monoterpene indole alkaloids, rauvines A and B, and six known derivatives were obtained from the leaves of R. vomitoria. The structures of rauvines A and B were determined by extensive spectroscopic analyses, 13 C-NMR, and ECD calculations. This is the first time to determine the absolute configurations of yohimbine-type N-oxides by quantum chemistry calculations (13 C-NMR and ECD calculations). All the isolates were tested for their cytotoxicity against five human cancer cell lines. Rauvine B showed moderate cytotoxicity on human MCF-7 breast, SWS80 colon, and A549 lung cancer cell lines with IC50 values of 25.5, 22.6, and 26.0 μM, respectively.
- Published
- 2020
27. Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model
- Author
-
Jia-kuan Liu, Shi-feng Yun, Tian Fang, Zesheng Xue, Meiqian Li, Di Wu, Jiaxuan Li, Yu-ting Song, and Jun Yan
- Subjects
Proliferation index ,H&E stain ,Prostatic Hyperplasia ,Pharmacology ,urologic and male genital diseases ,Rauwolfia ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Prostate ,medicine ,Animals ,Humans ,Aged ,biology ,business.industry ,Plant Extracts ,General Medicine ,Hyperplasia ,medicine.disease ,Proliferating cell nuclear antigen ,Rats ,Androgen receptor ,medicine.anatomical_structure ,chemistry ,Receptors, Androgen ,biology.protein ,Finasteride ,Quality of Life ,Immunohistochemistry ,Matrix Metalloproteinase 2 ,business ,Oxidoreductases - Abstract
Objective Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH. Methods Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured. Results The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. Conclusion R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
- Published
- 2020
28. In Vitro Studies on Antioxidant and Anti-Parasitic Activities of Compounds Isolated from Rauvolfia caffra Sond
- Author
-
Isaiah D. I. Ramaite, Dorcas B. Tlhapi, C. P. Anokwuru, Teunis van Ree, and Heinrich C. Hoppe
- Subjects
Antioxidant ,Rauvolfia caffra ,DPPH ,medicine.medical_treatment ,Trypanosoma brucei brucei ,Pharmaceutical Science ,antioxidant activity ,01 natural sciences ,Antioxidants ,Rauwolfia ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Column chromatography ,Drug Discovery ,medicine ,Rauvolfia caffra Sond ,Humans ,Physical and Theoretical Chemistry ,antitrypanosomal activity ,IC50 ,030304 developmental biology ,Lupeol ,0303 health sciences ,Chromatography ,bioactive compounds ,biology ,010405 organic chemistry ,Communication ,Organic Chemistry ,Biological activity ,biology.organism_classification ,Trypanocidal Agents ,0104 chemical sciences ,chemistry ,Chemistry (miscellaneous) ,Molecular Medicine ,Spegatrine ,HeLa Cells - Abstract
As part of an ongoing study of natural products from local medicinal plants, the methanol extract of stem bark of Rauvolfia caffra Sond was investigated for biological activity. Column chromatography and preparative thin-layer chromatography were used to isolate lupeol (1), raucaffricine (2), N-methylsarpagine (3), and spegatrine (4). The crude extract, fractions and isolated compounds were tested for anti-oxidant, antitrypanosomal and anti-proliferation activities. Two fractions displayed high DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity and reducing power with IC50 (The half maximal inhibitory concentration) and IC0.5 values of 0.022 ± 0.003 mg/mL and 0.036 ± 0.007 mg/mL, and 0.518 ± 0.044 mg/mL and 1.076 ± 0.136 mg/mL, respectively. Spegatrine (4) was identified as the main antioxidant compound in R. caffra with IC50 and IC0.5 values of 0.119 ± 0.067 mg/mL and 0.712 ± 0 mg/mL, respectively. One fraction displayed high antitrypanosomal activity with an IC50 value of 18.50 μg/mL. However, the major constituent of this fraction, raucaffricine (2), was not active. The crude extract, fractions and pure compounds did not display any cytotoxic effect at a concentration of 50 μg/mL against HeLa cells. This study shows directions for further in vitro studies on the antioxidant and antitrypanosomal activities of Rauvolfia caffra Sond.
- Published
- 2020
29. Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis
- Author
-
Yu-Xuan, Wang, Cheng, Lin, Lu-Jia, Cui, Wan-He, Yang, Qiu-Min, Li, Zhan-Ju, Liu, and Xin-Pu, Miao
- Subjects
Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,Cell Survival ,Plant Extracts ,Apoptosis ,Xenograft Model Antitumor Assays ,Rauwolfia ,Mice ,Cell Line, Tumor ,Autophagy ,Animals ,Humans ,Apoptosis Regulatory Proteins ,Colorectal Neoplasms - Abstract
Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined.Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth.Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo.Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.
- Published
- 2020
30. Peraksine derivatives with potential anti-inflammatory activities from the stems of Rauvolfia vomitoria
- Author
-
Guanqun Zhan, Zengjun Guo, Yu Zhang, Yingxu Zhang, Xinxin Zhang, Yi Hao, Rongkun Miao, Fuxin Zhang, and Muhammad Khurm
- Subjects
China ,medicine.drug_class ,Stereochemistry ,Monoterpene ,Phytochemicals ,Anti-Inflammatory Agents ,Nitric Oxide ,01 natural sciences ,Anti-inflammatory ,Rauwolfia ,Indole Alkaloids ,chemistry.chemical_compound ,Mice ,Drug Discovery ,medicine ,Animals ,Pharmacology ,Indole test ,Indole alkaloid ,Apocynaceae ,biology ,Molecular Structure ,Plant Stems ,010405 organic chemistry ,Chemistry ,Alkaloid ,Rauvolfia vomitoria ,General Medicine ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,RAW 264.7 Cells ,Pyran ,Monoterpenes - Abstract
Five new peraksine derivatives rauvomine C–G (1–5) along with four known analogues (6–9) were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). Structural determinations of the new monoterpene indole alkaloids were elucidated via comprehensive spectroscopic analyses and ECD calculations. Rauvomine C (1) with an unprecedented framework type represents the first example of C18 peraksine-type nor-monoterpene indole alkaloid featuring a chlorine atom at C-16 and its plausible biosynthetic pathway was also proposed. All the isolates were evaluated for their anti-inflammatory, cytotoxic, and acetylcholinesterase inhibitory activities. Among them, the new framework alkaloid rauvomine C (1) showed significant anti-inflammatory activities on NO production in LPS-induced RAW264.7 mouse macrophages with IC50 value of 10.76 μM. Additionally, peraksine-type alkaloids featuring pyran ring (5, 8, and 9) exhibited potential anti-inflammatory activities with IC50 values ranging from 17.52 to 20.99 μM.
- Published
- 2020
31. Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria
- Author
-
Hui Zhang, Lei Zhang, Guanqun Zhan, Gang Chang, Rongkun Miao, Xinxin Zhang, Zengjun Guo, and Fuxin Zhang
- Subjects
endocrine system ,Rauvolfia ,Monoterpene ,Molecular Conformation ,Crystallography, X-Ray ,complex mixtures ,01 natural sciences ,Biochemistry ,Rauwolfia ,Indole Alkaloids ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Humans ,heterocyclic compounds ,Molecular Biology ,Indole test ,Apocynaceae ,biology ,Indole alkaloid ,Dose-Response Relationship, Drug ,010405 organic chemistry ,organic chemicals ,Alkaloid ,Organic Chemistry ,Rauvolfia vomitoria ,Stereoisomerism ,biology.organism_classification ,Acetylcholinesterase ,0104 chemical sciences ,Molecular Docking Simulation ,Plant Leaves ,010404 medicinal & biomolecular chemistry ,chemistry ,Cholinesterase Inhibitors - Abstract
Seventeen monoterpene indole alkaloids, including seven new alkaloids (1−7) and ten known analogues (8−17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C22 yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2−3) and affinisine oxindole (5−6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2−3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1−17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 μM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC50 value of 16.39 ± 1.41 μM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were week inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.
- Published
- 2020
32. Phenolic constituents and inhibitory effects of the leaf of
- Author
-
Olubukola H, Oyeniran, Adedayo O, Ademiluyi, and Ganiyu, Oboh
- Subjects
Plant Leaves ,Free Radicals ,Phenols ,Plant Extracts ,Methanol ,Cholinergic Agents ,Animals ,Brain ,Antioxidants ,Rauwolfia ,Rats - Abstract
The polyphenols were evaluated by characterizing phenolic constituents using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The antioxidant properties were assessed through the extracts ability to reduce FeThe phenolic characterization ofThis study suggests that the rich phenolic constituents of
- Published
- 2020
33. Monoterpene indole alkaloids with diverse skeletons from the stems of Rauvolfia vomitoria and their acetylcholinesterase inhibitory activities
- Author
-
Rongkun Miao, Xincai Hao, Guanqun Zhan, Fuxin Zhang, Zengjun Guo, Xi Zheng, Hui Zhang, and Xinxin Zhang
- Subjects
0106 biological sciences ,endocrine system ,Aché ,Monoterpene ,Plant Science ,Horticulture ,complex mixtures ,01 natural sciences ,Biochemistry ,Rauwolfia ,Indole Alkaloids ,chemistry.chemical_compound ,heterocyclic compounds ,Cytotoxicity ,Molecular Biology ,Indole test ,biology ,Apocynaceae ,Molecular Structure ,010405 organic chemistry ,organic chemicals ,Alkaloid ,Rauvolfia vomitoria ,General Medicine ,biology.organism_classification ,Acetylcholinesterase ,language.human_language ,0104 chemical sciences ,chemistry ,language ,Monoterpenes ,Cholinesterase Inhibitors ,010606 plant biology & botany - Abstract
Nine undescribed monoterpene indole alkaloids, rauvomitorine A−I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kα radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 μM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors.
- Published
- 2020
34. Attenuation of potassium dichromate and sodium arsenite toxicities by methanol extract of
- Author
-
Kazeem A, Akinwumi, Michael A, Gbadegesin, Jumoke A, Aboyewa, and Oyeronke A, Odunola
- Subjects
Arsenites ,Plant Extracts ,Methanol ,Glutathione ,Sodium Compounds ,Antioxidants ,Rauwolfia ,Rats ,Mice ,Oxidative Stress ,Liver ,Animals ,Potassium Dichromate ,Rats, Wistar ,Biomarkers - Abstract
Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is paucity of information on reliable treatment modalilities. It is in this regard that this study evaluates the efficacy of methanol leaf extract ofSwiss albino mice between 7 and 10 weeks old were divided into eight cohorts of five animals each. Treatment groups consisted of a distilled water control, MRV alone (275 mg/kg po daily), KThe NaAsOMethanol extract of
- Published
- 2020
35. Expanding the Diversity of Plant Monoterpenoid Indole Alkaloids Employing Human Cytochrome P450 3A4
- Author
-
Yuriy V. Sheludko, Heribert Warzecha, Wolfgang Brandt, and Jascha Volk
- Subjects
Models, Molecular ,cytochromes ,CYP3A4 ,natural products ,Metabolite ,Molecular Conformation ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Rauwolfia ,Indole Alkaloids ,Substrate Specificity ,chemistry.chemical_compound ,Rauvolfia serpentina ,Cytochrome P-450 CYP3A ,Humans ,vinorine ,Molecular Biology ,Indole test ,Natural product ,biology ,Indole alkaloid ,010405 organic chemistry ,Chemistry ,Communication ,Organic Chemistry ,Cytochrome P450 ,Stereoisomerism ,Monooxygenase ,biology.organism_classification ,Secologanin Tryptamine Alkaloids ,Communications ,0104 chemical sciences ,Vomilenine ,biology.protein ,Molecular Medicine ,Epoxy Compounds ,monoterpenoid indole alkaloids - Abstract
Human drug‐metabolizing cytochrome P450 monooxygenases (CYPs) have enormous substrate promiscuity; this makes them promising tools for the expansion of natural product diversity. Here, we used CYP3A4 for the targeted diversification of a plant biosynthetic route leading to monoterpenoid indole alkaloids. In silico, in vitro and in planta studies proved that CYP3A4 was able to convert the indole alkaloid vinorine into vomilenine, the former being one of the central intermediates in the ajmaline pathway in the medicinal plant Rauvolfia serpentina (L.) Benth. ex Kurz. However, to a much larger extent, the investigated conversion yielded vinorine (19R,20R)‐epoxide, a new metabolite with an epoxide functional group that is rare for indole alkaloids. The described work represents a successful example of combinatorial biosynthesis towards an increase in biodiversity of natural metabolites. Moreover, characterisation of the products of the in vitro and in planta transformation of potential pharmaceuticals with human CYPs might be indicative of the route of their conversion in the human organism., Alternative oxidation: We used CYP3A4 for the targeted diversification of plant monoterpenoid indole alkaloids. In vitro and in planta studies proved that the cytochrome mainly converted vinorine into vinorine (19R,20R)‐epoxide, a new metabolite containing a rare for indole alkaloid epoxide group. A minor route led to the formation of the natural constituent vomilenine.
- Published
- 2020
36. CREM, PRM I and II gene expression in Wistar rats testes treated with antipsychotic drugs: Chlorpromazine, Rauwolfia vomitoria and co-administration of reserpine, zinc and ascorbic acid
- Author
-
Johnson Olawumi, Akingbade Adebanji, Adeleke Opeyemi, and Oyewopo Adeoye
- Subjects
Reserpine ,Chlorpromazine ,medicine.medical_treatment ,testes ,Gene Expression ,Ascorbic Acid ,Pharmacology ,Rauwolfia ,Cyclic AMP Response Element Modulator ,Testis ,Gene expression ,medicine ,Animals ,Humans ,Rats, Wistar ,Antipsychotic ,Saline ,Testosterone ,Rauwolfia vomitoria ,Plant Extracts ,business.industry ,Ascorbic acid ,Rats ,antipsychotics ,Zinc ,Original Article ,business ,Reproductive toxicity ,Antipsychotic Agents ,medicine.drug - Abstract
Objective The literature has shown that synthetic antipsychotic drugs induce reproductive toxicity, while psychiatric patients treated with traditionally used antipsychotic herbs (Rauwolfia vomitoria) showed no traces of reproductive toxicity. Thus, this study aimed to investigate the expression of CREM, PRM I and II genes in the testes of Wistar rats treated with antipsychotic drugs: chlorpromazine, Rauwolfia vomitoria (RV) and co-administration of reserpine, zinc and ascorbate (RAZ). Methods Forty-five adult male Wistar rats with rats with average weight of 180±4.67g were divided into nine groups (A-I) (n=5). Group A was administered saline (control) while rats in Groups B and C received 10 and 20mg/kg body weight (bwt) of chlorpromazine respectively. Groups D and E received 2.5 and 5mg/kg bwt of reserpine, respectively; while Groups F and G received 150 and 300mg/kg bwt of RV leaf extract. Groups H and I received (2.5+5+100) mg/kg bwt and (5+10+200) mg/kg of combination of RAZ, respectively for 56 days. Results The CREM, PRM I and II genes were significantly downregulated while significant decreased in serum FSH and testosterone concentration were found in the Chlorpromazine- and Reserpine-treated groups. Groups H and I showed a highly significant upregulation of the CREM, PRM I and II genes, and a highly significant increase in serum FSH and testosterone concentrations. Conclusion The study concluded that the HPT-Axis was impaired by chlorpromazine and reserpine, while RV and a combination of RAZ administration enhanced the axis in an animal model. The study recommended that synthetic antipsychotic drugs should be taken with Zinc and Ascorbate in order to help prevent reproductive toxicity associated with antipsychotic drugs. We need further studies in humans to confirm these findings.
- Published
- 2020
37. Overexpression of a Catharanthus tryptophan decarboxylase (tdc) gene leads to enhanced terpenoid indole alkaloid (TIA) production in transgenic hairy root lines of Rauwolfia serpentina.
- Author
-
Mehrotra, Shakti, Srivastava, Vikas, Rahman, Laiq Ur, and Kukreja, A. K.
- Abstract
To enhance the production of terpenoid indole alkaloids in Rauwolfia serpentina, Catharanthus tryptophan decarboxylase ( Crtdc) gene was over-expressed in transgenic hairy root cultures using Agrobacterium rhizogenes-mediated transformation. Among six transgenic hairy root lines, line RT4 accumulated the highest alkaloid content, with 0.1202 % dry weight (DW) reserpine and 0.0064 % DW ajmalicine, after 10 weeks of culture. Whereas, wild-type roots accumulated 0.0596 ± 0.003 % DW reserpine and 0.0011 ± 0.001 % DW ajmalicine. Transgenic hairy root line RT7 produced the lowest alkaloid content (reserpine: 0.0896 ± 0.002 % DW; ajmalicine: 0.002 ± 0.0 % DW). On the basis of alkaloid content the six hairy root lines were grouped as RT4/RT2 > RT3/RT5 > RT7/RT8. Analysis of gene expression profile indicated that Crtdc was expressed at a higher level in transgenic lines, which could be correlated with enhanced metabolite accumulation in roots. This study confirms that over-expression of Crtdc is a superlative method to improve the biosynthetic potential of Rauwolfia hairy root cultures. Enhanced reserpine and ajmalicine production can serve as an alternative choice to provide resources for relative pharmaceutical industries. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
38. Genus Rauvolfia: A review of its ethnopharmacology, phytochemistry, quality control/quality assurance, pharmacological activities and clinical evidence.
- Author
-
Kumar S, Kumari D, and Singh B
- Subjects
- Antihypertensive Agents therapeutic use, Ethnopharmacology, Humans, Indole Alkaloids, Phytochemicals analysis, Phytochemicals pharmacology, Phytochemicals therapeutic use, Phytotherapy, Plant Extracts chemistry, Plant Extracts pharmacology, Plant Extracts therapeutic use, Quality Control, Cardiovascular Diseases drug therapy, Plants, Medicinal, Rauwolfia
- Abstract
Ethnopharmacological Relevance: The plants are from the genus Rauvolfia Plum. ex L. (Apocynaceae), which is represented by 74 species with many synonyms, and distributed worldwide, especially in the Asian, and African continents. Traditionally, some of them are used for the treatment of various disorders related to the central nervous system (CNS), cardiovascular diseases (CVD), and as an antidote due to the presence of monoterpene indole alkaloids (MIAs) such as ajmaline (144), ajmalicine (164) serpentine (182), yohimbine (190) and reserpine (214)., Aim: The present review provides comprehensive summarization and critical analysis of the traditional to modern applications of Rauvolfia species, and the major focus was to include traditional uses, phytochemistry, quality control, pharmacological properties, as well as clinical evidence that may be useful in the drug discovery process., Materials and Methods: Information related to traditional uses, chemical constituents, separation techniques/analytical methods, and pharmacological properties of the genus Rauvolfia were obtained using electronic databases such as Web of Science, Scopus, SciFinder, PubMed, PubChem, ChemSpider, and Google Scholar between the years 1949-2021. The scientific name of the species and its synonyms were checked with the information of The Plant List., Results: A total of seventeen Rauvolfia species have been traditionally explored for various therapeutic applications, out of which the roots of R. serpentina and R. vomitoria are used most commonly for the treatment of many diseases. About 287 alkaloids, seven terpenoids, nine flavonoids, and four phenolic acids have been reported in different parts of the forty-three species. Quality control (QC)/quality assurance (QA) of extracts/herbal formulations of Rauvolfia species was analyzed by qualitative and quantitative methods based on the major MIAs such as compounds 144, 164, 182, 190, and 214 using HPTLC, HPLC, and HPLC-MS. The various extracts of different plant parts of thirteen Rauvolfia species are explored for their pharmacological properties such as antimicrobial, antioxidant, antiprotozoal, antitrypanosomal, antipsychotic, cardioprotective, cholinesterase inhibitory, and hepatoprotective. Of which, clinical trials of herbal formulations/extracts of R. serpentina and MIAs have been reported for CVD, CNS, antihypertensive therapy, antidiabetic effects, and psoriasis therapy, while the extracts and phytoconstituents of remaining Rauvolfia species are predominantly significant, owning them to be additional attention for further investigation under clinical trials and QC/QA., Conclusion: The present communication has provided a comprehensive, systematic, and critically analyzed vision into the traditional uses, phytochemistry, and modern therapeutic applications of the genus Rauvolfia are validated by scientific evidence. In addition, different plant parts from this genus, especially raw and finished herbal products of the roots of R. serpentina have been demonstrated for the QC/QA., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
39. Extracts of the Medicinal Plants Pao Pereira and Rauwolfia vomitoria Inhibit Ovarian Cancer Stem Cells In Vitro
- Author
-
Ping Chen, Ruochen Dong, and Qi Chen
- Subjects
Ovarian Neoplasms ,Plants, Medicinal ,Complementary and alternative medicine ,Oncology ,Plant Extracts ,Cell Line, Tumor ,Neoplastic Stem Cells ,Humans ,Female ,Rauwolfia ,beta Catenin ,Cell Proliferation - Abstract
Ovarian cancer has an enrichment of cancer stem cells (CSCs) which contribute to the treatment resistant tumor’s high rate of recurrence and metastasis. Here we investigated 2 plant extracts from the medicinal plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) each for their activities against ovarian CSCs. Both Pao and Rau inhibited overall proliferation of human ovarian cancer cell lines with IC50 ranging from 210 to 420 μg/mL and had limited cytotoxicity to normal epithelial cells. Ovarian CSC population was examined using cell surface markers and tumor spheroid formation assays. The results showed that both Pao and Rau treatment significantly reduced the ovarian CSC population. Pao and Rau had similar activities in inhibiting ovarian CSCs, with IC50s of ~120 μg/mL for 24 hours treatment, and ~50 μg/mL for long-term tumor spheroid formation. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. Taken together, data here showed that Pao and Rau both inhibited ovarian cancer stem cells, probably in preference to the bulk of tumor cells. Further mechanistic studies and in vivo investigation validating these findings are warranted, given that inhibition of cancer stem cells holds the promise of comprehensively inhibiting cancer metastasis, drug resistance and recurrence.
- Published
- 2022
40. Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission
- Author
-
Maria Júlia Sousa Fonseca, Norberto K.V. Monteiro, Kirley Marques Canuto, Otília Deusdênia L. Pessoa, Nilberto R.F. Nascimento, Luis Gustavo Farias De Sousa, Francisco Wagner de Queiroz Almeida Neto, Herbert S. Magalhães, Alison B. da Silva, and Maria Iracema Bezerra Loiola
- Subjects
Male ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Phytochemicals ,Neurotransmission ,In Vitro Techniques ,01 natural sciences ,Plant Roots ,Synaptic Transmission ,Rauwolfia ,Indole Alkaloids ,chemistry.chemical_compound ,Mice ,Vas Deferens ,Drug Discovery ,medicine ,Bioassay ,Animals ,heterocyclic compounds ,Neuroinhibitory effect ,Pharmacology ,Indole test ,Ethanol ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Plant Extracts ,Alkaloid ,Vas deferens ,General Medicine ,Carbon-13 NMR ,Electric Stimulation ,Rauvolfia ligustrina ,0104 chemical sciences ,Indole alkaloids ,010404 medicinal & biomolecular chemistry ,medicine.anatomical_structure ,GIAO 13C NMR ,Two-dimensional nuclear magnetic resonance spectroscopy ,Brazil - Abstract
The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.
- Published
- 2019
41. R. nukuhivensis acts by reinforcing skin barrier function, boosting skin immunity and by inhibiting IL-22 induced keratinocyte hyperproliferation
- Author
-
Chantal Pichon, Florence Abdallah, Gaël Lecellier, Phila Raharivelomanana, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Ecologie marine tropicale des océans Pacifique et Indien (ENTROPIE [Nouvelle-Calédonie]), Ifremer - Nouvelle-Calédonie, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Université de la Nouvelle-Calédonie (UNC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Ecosystèmes Insulaires Océaniens (UMR 241) (EIO), Université de la Polynésie Française (UPF)-Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Ifremer - Nouvelle-Calédonie, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Nouvelle-Calédonie (UNC), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Polynésie Française (UPF)-Institut Louis Malardé [Papeete] (ILM), and Institut de Recherche pour le Développement (IRD)
- Subjects
Keratinocytes ,0301 basic medicine ,Anti-Inflammatory Agents ,Cellular homeostasis ,lcsh:Medicine ,Inflammation ,Filaggrin Proteins ,Biology ,Article ,Rauwolfia ,Cell Line ,Interleukin 22 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,medicine ,Humans ,Skin immunity ,[CHIM]Chemical Sciences ,lcsh:Science ,Cell Proliferation ,Skin ,Multidisciplinary ,Innate immune system ,Plant Extracts ,Interleukins ,S100 Proteins ,lcsh:R ,PTEN Phosphohydrolase ,3. Good health ,Cell biology ,Toll-Like Receptor 5 ,030104 developmental biology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,lcsh:Q ,medicine.symptom ,Keratinocyte ,030217 neurology & neurosurgery - Abstract
Rauvolfia nukuhivensis is a well-known plant used for its wide range of beneficial effects in Marquesas islands. It is made up of diverse indole alkaloids and is used as traditional medicine for skin application. The actual mechanism behind the virtue of this plant is still unknown. Hence, in this study we aimed at deciphering the impact of R. nukuhivensis on skin immune system in context of (1) homeostasis, (2) pathogen infection and (3) inflammation. Here we show that R. nukuhivensis enhances cellular metabolic activity and wound healing without inducing cellular stress or disturbing cellular homeostasis. It reinforces the epithelial barrier by up-regulating hBD-1. Nevertheless, in pathogenic stress, R. nukuhivensis acts by preparing the immune system to be reactive and effective directly. Indeed, it enhances the innate immune response by increasing pathogens sensors such as TLR5. Finally, R. nukuhivensis blocks IL-22 induced hyperproliferation via PTEN and Filaggrin up-regulation as well as BCL-2 downregulation. In conclusion, this study provides evidence on the several cutaneous application potentials of R. nukuhivensis such as boosting the immune response or in restoring the integrity of the epithelial barrier.
- Published
- 2019
42. Bioactivity-Guided Isolation and Identification of New and Immunosuppressive Monoterpenoid Indole Alkaloids from
- Author
-
Li-Mei, Li, Shun-Dong, Shi, Yang, Liu, and Qiang, Zou
- Subjects
Reserpine ,Molecular Structure ,T-Lymphocytes ,monoterpenoid indole alkaloid ,immunosuppressive activity ,Secologanin Tryptamine Alkaloids ,Rauwolfia ,Article ,Inhibitory Concentration 50 ,11-hydroxyburnamine ,rauvoyunnanine B ,rauvoyunnanine A ,Humans ,Rauvolfia yunnanensis ,Cells, Cultured ,Immunosuppressive Agents ,Cell Proliferation - Abstract
Three new 11-hydroxyburnamine (1) and rauvoyunnanines A–B (2–3), and fourteen known (4–17) monoterpenoid indole alkaloids were isolated from the total alkaloids extract of Rauvolfia yunnanensis, which exhibited promising immunosuppressive activity on T cell proliferation in preliminary screening. Their structures were determined by analysis of high-resolution electrospray ionization mass (HRESIMS), ultraviolet (UV) and nuclear magnetic resonance (NMR) data, and by comparison with the literature. All the alkaloids were evaluated for inhibitory activity on T cell proliferation. Among them, one new compound (1) and reserpine (6) exhibited moderate immunosuppressive activity, with IC50 values of 5.9 μM and 5.0 μM, respectively.
- Published
- 2019
43. In vivo effects of Rauvolfia vomitoria ( Apocynaceae ) ethanolic extract on sexual performance and reproductive activity in male rats
- Author
-
Marie Ide Ngaha Njila, Alain Bertrand Dongmo, Hubert Kenmogne, Modeste Wankeu-Nya, Ijaz Bushra, Brice Landry Koloko, Doriane Camille Nyonseu Nzeubang, Dieudonné Massoma Lembè, Calvin Bogning Nzangueu, and Théophile Dimo
- Subjects
Male ,Sildenafil ,Ejaculation ,Urology ,030232 urology & nephrology ,Physiology ,Rauwolfia ,Sildenafil Citrate ,Sexual Behavior, Animal ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Testis ,medicine ,Animals ,030219 obstetrics & reproductive medicine ,Reproductive function ,Ethanol ,Sperm Count ,biology ,Apocynaceae ,Plant Extracts ,Rauvolfia vomitoria ,General Medicine ,biology.organism_classification ,medicine.disease ,Sperm ,Rats ,Erectile dysfunction ,chemistry ,Models, Animal ,Plant Bark ,Sperm Motility ,Urological Agents ,Female ,Spermatogenesis - Abstract
Plants and plant-derived products have a long history in the treatment of sexual disorders. Rauvolfia vomitoria is one of such plant used traditionally for the enhancement of male sexual and reproductive activity. This study was carried out to elucidate the potential activity of R. vomitoria ethanolic extract on sexual behaviour and male reproductive function. Twenty-five male rats were assigned to five groups and orally treated with distilled water (control), sildenafil citrate (standard) and R. vomitoria ethanolic extract (50, 100 and 200 mg/kg BW) for 22 days. Sexual behaviour parameters such as mount latency (ML), intromission latency (IL), ejaculation latency (EL), mount frequency (MF), intromission frequency (IF), ejaculation frequency (IF) and post-ejaculatory interval (PEI) were recorded at day 0, 1, 8, 15 and 22. The reproductive function including reproductive organ weights, testicular histology and sperm parameters was also assessed. Results showed enhancement in sexual behaviour through significant reduction (p < .01) in ML, IL and PEI and significant increase (p < .01) in EL, MF IF and EF. The extract also caused an increase in sperm count, motility and transit. Present findings demonstrate the ability of R. vomitoria ethanolic extract to improve male sexual behaviour and reproductive activity in rats.
- Published
- 2019
44. Simultaneous determination of intestinal permeability and potential drug interactions of complex mixtures using Caco-2 cells and high-resolution mass spectrometry: Studies with Rauwolfia serpentina extract
- Author
-
Sanah N. Vohra and Thomas J. Flynn
- Subjects
Drug ,Glucuronosyltransferase ,media_common.quotation_subject ,Glucuronidation ,Toxicology ,030226 pharmacology & pharmacy ,Mass Spectrometry ,Permeability ,Rauwolfia ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,0302 clinical medicine ,Rauwolfia alkaloid ,Corynanthine ,Cytochrome P-450 CYP3A ,Humans ,Intestinal Mucosa ,Chromatography, High Pressure Liquid ,media_common ,Chromatography ,CYP3A4 ,biology ,Plant Extracts ,Chemistry ,General Medicine ,Bioavailability ,Glucuronosyltransferase activity ,030220 oncology & carcinogenesis ,biology.protein ,Caco-2 Cells - Abstract
Caco-2 cells are a commonly used model for estimating the intestinal bioavailability of single chemical entity pharmaceuticals. Caco-2 cells, when induced with calcitriol, also express other biological functions such as phase I (CYP) and phase II (glucuronosyltransferases) drug metabolizing enzymes which are relevant to drug-supplement interactions. Intestinal bioavailability is an important factor in the overall safety assessment of products consumed orally. Foods, including herbal dietary supplements, are complex substances with multiple chemical components. Because of potential interactions between components of complex mixtures, more reliable safety assessments can be obtained by studying the commercial products “as consumed” rather than by testing individual chemical components one at a time. The present study evaluated the apparent intestinal permeability (Papp) of a model herbal extract, Rauwolfia serpentina, using both whole plant extracts and the individual purified Rauwolfia alkaloids. All test compounds, endpoint substrates, and their metabolites were quantified using liquid chromatography and high-resolution mass spectrometry. The Papp values for individual Rauwolfia alkaloids were comparable whether measured individually or as components of the complete extract. Both Rauwolfia extract and all individual Rauwolfia alkaloids except yohimbine inhibited CYP3A4 activity (midazolam 1′-hydroxylation). Both Rauwolfia extract and all individual Rauwolfia alkaloids except corynanthine and reserpic acid significantly increased glucuronosyltransferase activity (glucuronidation of 4-methylumbelliferone). The positive control, ketoconazole, significantly inhibited both CYP3A4 and glucuronosyltransferase activities. These findings suggest that the Caco-2 assay is capable of simultaneously identifying both bioavailability and potentially hazardous intestinal drug-supplement interactions in complex mixtures.
- Published
- 2018
45. Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes
- Author
-
Jakob Franke, Chloe Langley, Thu-Thuy T. Dang, Vincent Courdavault, Inês Carqueijeiro, Sarah E. O'Connor, John Innes Centre [Norwich], Biomolécules et biotechnologies végétales (BBV EA 2106), and Université de Tours (UT)
- Subjects
0106 biological sciences ,0301 basic medicine ,Cytochrome ,Stereochemistry ,Catharanthus ,Monoterpene ,[SDV]Life Sciences [q-bio] ,Molecular Conformation ,01 natural sciences ,Article ,Rauwolfia ,Indole Alkaloids ,Substrate Specificity ,03 medical and health sciences ,Cytochrome P-450 Enzyme System ,heterocyclic compounds ,Molecular Biology ,Indole test ,chemistry.chemical_classification ,biology ,Chemistry ,Aromatization ,Substrate (chemistry) ,Stereoisomerism ,Cell Biology ,Catharanthus roseus ,biology.organism_classification ,Gelsemium ,030104 developmental biology ,Enzyme ,Cyclization ,biology.protein ,010606 plant biology & botany - Abstract
International audience; Cyclization reactions that create complex polycyclic scaffolds are hallmarks of alkaloid biosynthetic pathways. We present the discovery of three homologous cytochrome P450s from three monoterpene indole alkaloid-producing plants (Rauwolfia serpentina, Gelsemium sempervirens and Catharanthus roseus) that provide entry into two distinct alkaloid classes, the sarpagans and the β-carbolines. Our results highlight how a common enzymatic mechanism, guided by related but structurally distinct substrates, leads to either cyclization or aromatization.
- Published
- 2018
46. Anti-seizure activity of African medicinal plants: The identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model
- Author
-
Talent Chipiti, Weiyang Chen, Alexander D. Crawford, Gill M. Enslin, Maxleene Sandasi, Maria Lorena Cordero-Maldonado, Clinton G. L. Veale, Alvaro M. Viljoen, and Fanie R. van Heerden
- Subjects
Male ,Drug ,Rauvolfia caffra ,media_common.quotation_subject ,Rauwolfia ,South Africa ,03 medical and health sciences ,chemistry.chemical_compound ,Epilepsy ,Alkaloids ,0302 clinical medicine ,Seizures ,In vivo ,Drug Discovery ,medicine ,Animals ,Medicinal plants ,Medicine, African Traditional ,Zebrafish ,030304 developmental biology ,media_common ,Pharmacology ,0303 health sciences ,Plants, Medicinal ,biology ,Traditional medicine ,Plant Extracts ,Alkaloid ,biology.organism_classification ,medicine.disease ,High-Throughput Screening Assays ,Disease Models, Animal ,chemistry ,Larva ,030220 oncology & carcinogenesis ,Anticonvulsants ,Female ,Tryptoline - Abstract
Ethnopharmacological relevance Epilepsy is one of the major chronic diseases that does not have a cure to date. Adverse drug reactions have been reported from the use of available anti-epileptic drugs (AEDs) which are also effective in only two-thirds of the patients. Accordingly, the identification of scaffolds with promising anti-seizure activity remains an important first step towards the development of new anti-epileptic therapies, with improved efficacy and reduced adverse effects. Herbal medicines are widely used in developing countries, including in the treatment of epilepsy but with little scientific evidence to validate this use. In the search for new epilepsy treatment options, the zebrafish has emerged as a chemoconvulsant-based model for epilepsy, mainly because of the many advantages that zebrafish larvae offer making them highly suitable for high-throughput drug screening. Aim of the study In this study, 20 medicinal plants traditionally used in South Africa to treat epilepsy were screened for anti-epileptic activity using a zebrafish larvae model. Materials and methods Toxicity triaging was conducted on 120 crude extracts, 44 fractions and three isolated compounds to determine the maximum tolerated concentration (MTC) of each extract, fraction or compound. MTC values were used to guide the concentration range selection in bioactivity studies. The effectiveness of crude extracts, fractions and isolated compounds from Rauvolfia caffra Sond. in suppression of pentylenetetrazole (PTZ) induced seizure-like behaviour in a 6-dpf zebrafish larvae model was measured using the PTZ assay. Results Following a preliminary toxicity triage and bioactivity screen of crude extracts from 20 African plants used traditionally for the treatment and management of epilepsy, the methanolic extract of Rauvolfia caffra Sond. was identified as the most promising at suppressing PTZ induced seizure-like behaviour in a zebrafish larvae model. Subsequent bioactivity-guided fractionation and spectroscopic structural elucidation resulted in the isolation and identification of two tryptoline derivatives; a previously unreported alkaloid to which we assigned the trivial name rauverine H (1) and the known alkaloid pleiocarpamine (2). Pleiocarpamine was found to reduce PTZ-induced seizures in a dose-dependent manner. Conclusions Accordingly, pleiocarpamine represents a promising scaffold for the development of new anti-seizure therapeutic compounds. Furthermore , the results of this study provide preliminary evidence to support the traditional use of Rauvolfia caffra Sond. in the treatment and management of epilepsy. These findings warrant further studies on the anti-epileptic potential of Rauvolfia caffra Sond. using other models.
- Published
- 2021
47. Molecular and chemical characterization of plants regenerated from Ri-mediated hairy root cultures of Rauwolfia serpentina.
- Author
-
Mehrotra, Shakti, Goel, Manoj, Rahman, Laiq, and Kukreja, A.
- Abstract
Hairy root lines were induced from leaf explants of Rauwolfia serpentina known to contain high levels of reserpine (0.0882 % DW) content. Out of five high yielding hairy root lines, three (R1, R14 and R15) exhibited spontaneous regeneration of shoots after 6-8 weeks in liquid B5 medium. Excised regenerated shoots underwent robust shoot proliferation when cultured on Murashige and Skoog (MS) medium supplemented with 0.1 mg/l naphthanleneacetic acid (NAA) and 1.0 mg/l 6-benzyladenine. When shoots were transferred to a root induction medium, consisting of MS basal medium and 1.0 mg/l NAA, all rooted within 2-3 weeks. Of a total of 45 plants developed from three different hairy root lines, 30 were successfully acclimatized and transferred to the green house. Almost 90 % of these plants grown in the green house showed no observed phenotypic differences, while 10 % were stunted and grew poorly, in comparison to non-transformed plants. Phenotypic assessment of regenerated plants for plant length, number of nodes and intermodal lengths, number of leaves per node, leaf color, leaf size, number of flowering shoots, flower size, fruit size, lateral root branching and root biomass was conducted. Polymerase chain reaction and Southern blot hybridization revealed that all plants derived from hairy roots carried the Ri T-DNA fragment. Moreover for plants derived from transgenic hairy root line R14, presence of more than a single transgene copy number was observed, and this might have contributed to observed abnormal phenotypes. Analysis of reserpine content revealed that roots of regenerated plants had similar levels (0.0889 % DW) to those of their corresponding hairy roots. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
48. Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress.
- Author
-
Huang G, He X, Xue Z, Long Y, Liu J, Cai J, Tang P, Han B, Shen B, Huang R, and Yan J
- Subjects
- Animals, Apoptosis, Autophagy, Endoplasmic Reticulum Stress, Humans, Male, Rats, Prostatic Hyperplasia drug therapy, Rauwolfia
- Abstract
Background: The current drug treatments for benign prostatic hyperplasia (BPH) have negative side effects. Therefore, it is important to find effective alternative therapies with significantly fewer side effects. Our previous study revealed that Rauwolfia vomitoria (RWF) root bark extract reversed BPH development in a rat model. However, the molecular mechanism of its inhibitory effects on BPH remains largely unknown., Methods: BPH-1 and WPMY-1 cell lines derived from BPH epithelial and prostatic stromal compartments were selected to investigate how RWF extract inhibits BPH in vitro by MTT and flow cytometry assays. Microarray, quantitative real-time PCR, immunoblotting, and GFP-LC3 immunofluorescence assays were performed to evaluate the effects of RWF extract on endoplasmic reticulum stress (ER stress) and autophagic apoptosis pathways in two cell lines. A human BPH ex vivo explant assay was also employed for validation., Results: RWF extract treatment decreased cell viability and induced apoptotic cell death in both BPH-1 and WPMY-1 cells in a concentration-dependent manner with the increase of pro-apoptotic PCDC4 protein. RWF extract induced autophagy by enhancing the levels of autophagic genes (ULK2 and SQSTM1/p62) and the LC3II:LC3I ratio, with the increase of GFP-LC3 puncta. Moreover, RWF extract activated PERK- and ATF6-associated ER stress pathways by inducing the transcriptional levels of EIF2AK3/PERK, DDIT3/CHOP and ATF6, accompanied by the reduction of BiP protein level, but not its mRNA level. Another ER stress pathway was not induced by RWF extract, as manifested by the lack of XBP1 splicing. Pharmacological inhibition of autophagy by 3-methyladenine abrogated apoptosis but not ER stress; while inhibition of ER stress by 4-phenylbutyrate alleviated the induction of autophagy and apoptosis. In addition, pretreatments with either 3-methyladenine or 4-phenylbutyrate suppressed RWF extract-induced cytotoxicity. Notably, the inductions of PERK- and ATF6-related stress pathways and autophagic apoptosis were confirmed in a human BPH ex vivo explant., Conclusions: Our data have demonstrated that RWF extract significantly suppressed the viabilities of BPH epithelial cells and BPH myofibroblasts by inducing apoptosis via upregulating ER stress and autophagy. These data indicate that RWF extract is a potential novel alternative therapeutic approach for BPH., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
49. Influence of Inoculation with the Endomycorrhizal Fungi and Trichoderma viride on Morphological and Physiological Growth Parameters of Rauwolfia serpentina Benth. Ex. Kurtz.
- Author
-
Kaushish, Sunita, Kumar, Aditya, Aggarwal, Ashok, and Parkash, Vipin
- Subjects
- *
MYCORRHIZAL fungi , *GLOMUS mosseae , *TRICHODERMA viride , *RAUVOLFIA serpentina , *VESICULAR-arbuscular mycorrhizas , *PLANT inoculation , *PHOSPHORUS , *CHEMICAL composition of plants - Abstract
Two arbuscular mycorrhizal fungi, Glomus mosseae and Acaulospora laevis either alone or in combination with Trichoderma viride showed the dependence of Rauwolfia serpentina on endomycorrhizal fungi. After 60 days, G. mosseae singly or in combination with Trichoderma viride showed enhanced height increment compared to control plants. Maximum phosphorus content was shown by plants treated with G. mosseae plus T. viride (0.444 ± 2.62) in roots and (0.437 ± 4.71) in shoots. Phosphorus content in roots was more than that in shoots. Chlorophyll content and stomatal conductivity also showed similar trend. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
50. Dual Catalytic Activity of a Cytochrome P450 Controls Bifurcation at a Metabolic Branch Point of Alkaloid Biosynthesis in Rauwolfia serpentina
- Author
-
Jakob Franke, Sarah E. O'Connor, Thu-Thuy T. Dang, and Evangelos C. Tatsis
- Subjects
0106 biological sciences ,0301 basic medicine ,Stereochemistry ,Molecular Conformation ,010402 general chemistry ,Biosynthesis ,01 natural sciences ,Catalysis ,Rauwolfia ,cytochrome p450s ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,Cytochrome P-450 Enzyme System ,Rauvolfia serpentina ,medicine ,vomilenine ,perakine ,chemistry.chemical_classification ,biology ,Communication ,Ajmalan ,Cytochrome P450 ,food and beverages ,General Medicine ,General Chemistry ,biology.organism_classification ,Communications ,0104 chemical sciences ,Ajmaline ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,Vomilenine ,biology.protein ,Biocatalysis ,Epimer ,010606 plant biology & botany ,medicine.drug - Abstract
Plants create tremendous chemical diversity from a single biosynthetic intermediate. In plant‐derived ajmalan alkaloid pathways, the biosynthetic intermediate vomilenine can be transformed into the anti‐arrhythmic compound ajmaline, or alternatively, can isomerize to form perakine, an alkaloid with a structurally distinct scaffold. Here we report the discovery and characterization of vinorine hydroxylase, a cytochrome P450 enzyme that hydroxylates vinorine to form vomilenine, which was found to exist as a mixture of rapidly interconverting epimers. Surprisingly, this cytochrome P450 also catalyzes the non‐oxidative isomerization of the ajmaline precursor vomilenine to perakine. This unusual dual catalytic activity of vinorine hydroxylase thereby provides a control mechanism for the bifurcation of these alkaloid pathway branches. This discovery highlights the unusual catalytic functionality that has evolved in plant pathways.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.