167 results on '"Conessine"'
Search Results
2. Conessine alleviates PTZ-induced epilepsy in rat model via attenuating neuroinflammation and oxidative stress
- Author
-
Fang Chen, Tingting Peng, and Mengjiao Gou
- Subjects
Epilepsy ,Seizures ,Neuroinflammation ,Oxidative stress ,Conessine ,Chemistry ,QD1-999 - Abstract
Epilepsy is a complex neurological disorder which affects the quality life of individual and also hinders the economic status of both the individuals and the country since it requires prolonged medications. The etiology of epilepsy is varied and the neuroinflammation has been considered to be the prime initiator and the stimulator of the disease progression. Therefore anti-inflammatory drugs are suggested to treat seizure and also to prevent epilepsy. The currently available antiepileptic drugs cause’s adverse effects which obstructs the usage of these drugs and also these drugs are not cost effective. Phytochemicals are effective alternative to these drugs and it is prescribed in the traditional medicine. Conessine, a steroidal alkaloid present in bark extracts of Holarrhena sps possess antibiotic, anti-diarrheal, antimalarial and anti-inflammatory properties. We evaluated the antiepileptic potency of conessine in PTZ challenged animal model treated with 10 and 20 mg/kg of conessine respectively. The seizure induction, severity and the behavioral changes were observed in the rats. The impact of conessine on neurochemical signaling in PTZ challenged rats were assessed via quantifying the neurotransmitter and ATPase levels in the brain tissue. Antioxidants and MDA levels were measured to evaluate the antioxidant potency of conessine in epilepsy induced rats. iNOS and nNOS which are inducers of NO during epileptic conditions were analyzed in the test rats. The stimulators and inflammatory cytokines levels were quantified in the brain to analyze the anti-neuroinflammatory efficacy of the conessine in PTZ challenged rats. AKT/mTOR prime signaling proteins in initiation and progression of epilepsy was quantified in the brain tissue of experimental animals. Neurodegeneration inducers cytochrome c, NF-κB, COX-2 and Caspase 3 were quantified to evaluate the ameliorative potency of conessine against PTZ induced neuronal damage. The neuroprotective and antiepileptic potency of conessine was confirmed with the histopathological scoring of brain tissue in PTZ challenged rats. Conessine treatment effectively inhibited the seizure induction and regulated the neurochemical signaling in epileptic induced rats. It also attenuated the neuroinflammation and oxidative stress induction induced by PTZ treatment. The prime signaling proteins nitric oxide synthatase and AKT/mTOR signaling proteins were effectively inhibited by the conessine treatment which eventually prevented the neurodegeneration inducers. Conessine treatment significantly enhanced the levels of Caspase 3. The histopathological analysis confirms the neuroprotective, anti-inflammatory and antiepileptic potency of conessine. Conessine treatment also doesn’t caused any behavioral alterations in the rats hence it is safe and potent alternative for currently available antiepileptic drugs.
- Published
- 2024
- Full Text
- View/download PDF
3. Conessine inhibits enveloped viruses replication through up-regulating cholesterol level
- Author
-
Shili Zhou, Jie Li, Xiaomei Ling, Shirui Dong, Zhen Zhang, and Ming Li
- Subjects
Conessine ,Cholesterol ,Dengue virus (DENV) ,Enveloped virus ,Microbiology ,QR1-502 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Dengue virus (DENV) is one of the most prevalent arthropod-borne diseases. It may cause dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), while no effective vaccines and drugs are available. Our study demonstrated that conessine exhibits broad antiviral activity against several enveloped viruses, including DENV, vesicular stomatitis virus, and herpes simplex virus. In addition, conessine has no direct destructive effect on the integrity or infectivity of virions. Both pre-treatment and post-treatment with conessine significantly reduce DENV replication. Pre-treatment with conessine disrupts the endocytosis of enveloped viruses, while post-treatment disturbs DENV RNA replication or translation at an early stage. Through screening differentially expressed genes by transcriptome sequencing, we found that conessine may affect cholesterol biosynthesis, metabolism or homeostasis. Finally, we confirmed that conessine inhibits virus replication through up-regulating cholesterol levels. Our work suggests that conessine could be developed as a prophylactic and therapeutic treatment for infectious diseases caused by enveloped viruses.
- Published
- 2023
- Full Text
- View/download PDF
4. Modulation in the enzymatic antioxidants, MDA level and elicitation in conessine biomolecule in Holarrhena pubescens (medicinal tree) cultures exposed to different heavy metals: Ni, Co, Cr and As.
- Author
-
Kumar, Dinesh, Kumar, Ravindra, Singh, Bharat, and Agrawal, Veena
- Subjects
- *
GLUTATHIONE peroxidase , *HEAVY metals , *BIOACTIVE compounds , *SUPEROXIDE dismutase - Abstract
Nodal explants of Holarrhena pubescens, an important medicinal tree, were cultured on Murashige and Skoog's medium (MS) containing 15 µM BA (control) alone and on medium supplemented with different concentrations (0, 1, 5, 25, 50, 100 and 200 mg/L) of heavy metals such as NiCl2, CoCl2, As2O3 and CrO3 to study their toxic effect. After 28 days of treatments, the nodal segments were harvested to assess the average number of shoots per explants, average shoot length, malondialdehyde content, proline content, conessine accumulation and antioxidant enzymatic activity. Among all the metals tried, best morphogenic response was achieved at 5 mg/L CrO3 where 80% culture differentiated an average of 3.21 ± 0.08 shoots per explant having 0.95 ± 0.018 cm average shoot length. Highest concentration (200 mg/L) of all the heavy metals proved lethal for morphogenesis. Maximum inhibition in average shoot number and average shoot length was observed in nodal explants treated with 25 mg/L As2O3 where an average of 0.49 ± 0.047 shoots having an average shoot length of 0.3 ± 0.02 cm. Contrarily, addition of heavy metals in culture medium proved strong elicitors, exhibiting significant enhancement in the biosynthesis of conessine, an important bioactive compound. HPLC analysis of the crude extract of in vitro grown untreated nodal cultures revealed an average of 117.06 ± 2.59 µg/g d. w. of conessine, whereas those treated with 100 mg/L of CoCl2 accounted for 297.1 ± 7.76 µg/g d. w. (an increase of 156% over control). Among the heavy metals tried, CoCl2 proved to be the best for conessine enhancement which was in the order of CoCl2 > Cr2O3 > NiCl2 > As2O3 in the nodal explants. Concomitantly, MDA content, the antioxidant enzymes activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GR) and ascorbate peroxidase (APX) were also observed to be differentially expressed with the increase in the heavy metals concentration from 1 to 200 mg/L. Free proline, too, increased up to 3.5-fold over control. The results obtained during the present investigation revealed that the overall response of the nodal explants in terms of morphogenesis, conessine content and antioxidant enzyme activities was metal specific as well as dose dependent. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Steroidal Alkaloids From the Apocynaceae Family: Their Isolation and Biological Activity.
- Author
-
Abd Karim, Hidayatul Atiqah, Ismail, Nor Hadiani, and Osman, Che Puteh
- Subjects
STEROIDAL alkaloids ,APOCYNACEAE ,ISOQUINOLINE alkaloids ,DRUG discovery ,ALKALOIDS ,PREGNANE ,ANABOLIC steroids ,PLANT species - Abstract
Steroidal alkaloids are derived from the steroid skeleton with one or two nitrogen atoms. They are widely distributed in tropical and subtropical regions and possess a range of biological activities. The structures of steroidal alkaloids are comparable to those of anabolic steroids, steroidal hormones, and corticosteroids, making them a valuable source for drug discovery. Taxonomically, steroidal alkaloids are limited in distribution to certain plant families, predominantly the Apocynaceae, Buxaceae, Solanaceae, and Liliaceae. This review highlights the steroidal alkaloids from the Apocynaceae family and their biological activities. The articles published from 1919 to 2021 were included in this review. A total of 163 steroidal alkaloids and 12 biological activities were reported from plant species belonging to the Apocynaceae family in this period. Of the 410 genera in the Apocynaceae, only 10 contain steroidal alkaloids. Although some alkaloids from the Apocynaceae family were also reported in the Buxaceae family, especially tetracyclic triterpenes with a pregnane side chain, most steroidal alkaloids can only be found in several genera of the Apocynaceae family. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
6. Neuroprotective effect of Conessinin on Elevated oxidative stress induced Alzheimers'disease in rats
- Author
-
Bandaru, Nagaraju, Komavari, Chandrasekhar, Gorla, Uma Sankar, Koteswarao, GSN, Kulandaivelu, Umasankar, and Ankarao, A.
- Published
- 2020
- Full Text
- View/download PDF
7. Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection
- Author
-
Thanyaluck Siriyong, Supayang Piyawan Voravuthikunchai, and Peter John Coote
- Subjects
Conessine ,Efflux pump inhibitor ,Galleria mellonella ,Holarrhena antidysenterica ,Mex efflux systems ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background This study aimed to evaluate the efficacy of combinations of steroidal alkaloids and conessine from the Thai medicinal plant Holarrhena antidysenterica with antibiotics against Pseudomonas aeruginosa strains possessing different efflux-pump-mediated multidrug-resistant (MDR) phenotypes in a Galleria mellonella infection model. Methods P. aeruginosa strains with defined mutations that result in the overexpression of the MexAB-OprM, MexCD-OprJ and MexEF-OprN efflux pumps, and a strain with all three of these pumps deleted, were used. In vitro, the effect of combinations of steroidal alkaloids and conessine with antibiotics was compared with antibiotic treatment alone via MIC determination and time-kill assays. Efficacy of combinations of the steroidal alkaloids and conessine with levofloxacin were compared with monotherapies against infections in G. mellonella larvae by measuring larval mortality and bacterial burden. Results Combination therapies of conessine or steroidal alkaloids with levofloxacin enhanced bacterial inhibition in vitro and restored antibiotic efficacy in vivo compared to the constituent monotherapies. Neither conessine nor the steroidal alkaloids induced any detectable toxicity in G. mellonella larvae. The enhanced efficacy of the combination treatments was most pronounced with conessine and correlated with reduced larval burden of infecting P. aeruginosa. Notably, the enhanced efficacy of conessine/levofloxacin combinations was only detected in the parent strain and strains that overexpressed the MexAB-OprM or MexEF-OprN efflux systems. Conclusions Steroidal alkaloids from Holarrhena antidysenterica, and particularly the principal active ingredient conessine, restored levofloxacin efficacy against resistant P. aeruginosa strains possessing efflux-mediated MDR phenotypes. The compounds should be investigated further as a potential novel therapy.
- Published
- 2018
- Full Text
- View/download PDF
8. Determination of Histamine H3-Receptor Antagonist Conessine in Wistar Rat Plasma by a Rapid and Sensitive RP-UFLC Method: Application to a Pharmacokinetic Study.
- Author
-
Ambhore, Nilesh Sudhakar, Raju Kalidhindi, Rama Satyanarayana, Mohire, Shubhashri, Yamjala, Karthik, Mulukutla, Shashank, Murthy, Vishakantha, Thondawada, Mahesh, and Elango, Kannan
- Subjects
- *
ANTIHISTAMINES , *CENTRAL nervous system , *PARKINSON'S disease , *BASAL ganglia , *SULFONIC acids - Abstract
Objectives: Epidemiological data suggests the highest density of histamine H3-receptors (H3R) in basal ganglia of central nervous system (CNS) wherein they function as inhibitory auto-receptors and control the release of many neurotransmitters. Inhibition of H3R increases the turnover of neurotransmitters, especially dopamine in basal ganglia and could be beneficial to treat Parkinson’s disease. Methods: In this study, we formulated the brain targeting liposomes of conessine, a selective antagonist for H3R to increase bioavailability and developed and validated a rapid and sensitive reverse phase ultra-force liquid chromatographic (RP-UFLC) method and to quantitate conessine in Wistar rat plasma and tissue. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and aripiprazole as the internal standard. Chromatographic separation was performed on the Hibar C18 column with a mobile phase of Hexane Sulphonic acid (10 mM, pH 10.0 adjusted with ammonia) and methanol at a flow rate of 0.9 ml/min. Results: The lower limit of quantification of the developed method was 4.0 ng/ml and 6.0 ng/g in plasma and tissue samples, respectively. Liposomes of conessine (equivalent to 20 mg/kg) administered orally to animals, demonstrated remarkable absorption into the systemic circulation with maximum concentration (~8700 ng/ml) within 2.0 h. The order of area under curve was found to be kidney> brain> liver> lungs> spleen> heart. Conclusion: The liposomes of conessine were rapidly taken up into the brain and showed a good brain concentration after 2.0 h; sustenance up to 4.0 h was achieved which is better than conessine solution. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
9. Conessine inhibits enveloped viruses replication through up-regulating cholesterol level.
- Author
-
Zhou, Shili, Li, Jie, Ling, Xiaomei, Dong, Shirui, Zhang, Zhen, and Li, Ming
- Subjects
- *
DENGUE hemorrhagic fever , *VIRAL replication , *DENGUE viruses , *CHOLESTEROL , *HERPES simplex virus - Abstract
• Conessine inhibits the replication of several enveloped viruses, including Dengue virus. • Conessine disrupts the endocytosis and RNA replication or translation of Dengue virus. • Conessine inhibits DENV replication through up-regulating cholesterol level. Dengue virus (DENV) is one of the most prevalent arthropod-borne diseases. It may cause dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), while no effective vaccines and drugs are available. Our study demonstrated that conessine exhibits broad antiviral activity against several enveloped viruses, including DENV, vesicular stomatitis virus, and herpes simplex virus. In addition, conessine has no direct destructive effect on the integrity or infectivity of virions. Both pre-treatment and post-treatment with conessine significantly reduce DENV replication. Pre-treatment with conessine disrupts the endocytosis of enveloped viruses, while post-treatment disturbs DENV RNA replication or translation at an early stage. Through screening differentially expressed genes by transcriptome sequencing, we found that conessine may affect cholesterol biosynthesis, metabolism or homeostasis. Finally, we confirmed that conessine inhibits virus replication through up-regulating cholesterol levels. Our work suggests that conessine could be developed as a prophylactic and therapeutic treatment for infectious diseases caused by enveloped viruses. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
10. Conessine as a novel inhibitor of multidrug efflux pump systems in Pseudomonas aeruginosa
- Author
-
Thanyaluck Siriyong, Potjanee Srimanote, Sasitorn Chusri, Boon-ek Yingyongnarongkul, Channarong Suaisom, Varomyalin Tipmanee, and Supayang Piyawan Voravuthikunchai
- Subjects
Conessine ,Efflux pump inhibitor ,MexAB-OprM efflux system ,Pseudomonas aeruginosa ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background Holarrhena antidysenterica has been employed as an ethnobotanical plant for the treatment of dysentery, diarrhoea, fever, and bacterial infections. Biological activities of the principle compound, conessine including anti-diarrhoea and anti-plasmodial effects were documented. Our previous study reported potency of Holarrhena antidysenterica extract and conessine as resistance modifying agents against extensively drug-resistant Acinetobacter baumannii. This study aimed to investigate (i) whether conessine, a steroidal alkaloid compound, could act as a resistance modifying agent against multidrug-resistant Pseudomonas aeruginosa, and (ii) whether MexAB-OprM efflux pump involved in the mechanism. Methods Conessine combined with various antibiotics were determined for synergistic activity against P. aeruginosa PAO1 strain K767 (wild-type), K1455 (MexAB-OprM overexpressed), and K1523 (MexB deletion). H33342 accumulation assay was used to evaluate efflux pump inhibition while NPN uptake assay was assessed membrane permeabilization. Results Conessine significantly reduced MICs of all antibiotics by at least 8-fold in MexAB-OprM overexpressed strain. The levels were comparable to those obtained in wild-type strain for cefotaxime, levofloxacin, and tetracycline. With erythromycin, novobiocin, and rifampicin, MICs were 4- to 8-fold less than MICs of the wild-type strain. Loss of MexAB-OprM due to deletion of mexB affected susceptibility to almost all antibiotics, except novobiocin. Synergistic activities between other antibiotics (except novobiocin) and conessine observed in MexB deletion strain suggested that conessine might inhibit other efflux systems present in P. aeruginosa. Inhibition of H33342 efflux in the tested strains clearly demonstrated that conessine inhibited MexAB-OprM pump. In contrast, the mode of action as a membrane permeabilizer was not observed after treatment with conessine as evidenced by no accumulation of 1-N-phenylnaphthylamine. Conclusions The results suggested that conessine could be applied as a novel efflux pump inhibitor to restore antibiotic activity by inhibiting efflux pump systems in P. aeruginosa. The findings speculated that conessine may also have a potential to be active against homologous resistance–nodulation–division (RND) family in other Gram-negative pathogens.
- Published
- 2017
- Full Text
- View/download PDF
11. Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection.
- Author
-
Siriyong, Thanyaluck, Voravuthikunchai, Supayang Piyawan, and Coote, Peter John
- Abstract
Background: This study aimed to evaluate the efficacy of combinations of steroidal alkaloids and conessine from the Thai medicinal plant Holarrhena antidysenterica with antibiotics against Pseudomonas aeruginosa strains possessing different efflux-pump-mediated multidrug-resistant (MDR) phenotypes in a Galleria mellonella infection model. Methods: P. aeruginosa strains with defined mutations that result in the overexpression of the MexAB-OprM, MexCD-OprJ and MexEF-OprN efflux pumps, and a strain with all three of these pumps deleted, were used. In vitro, the effect of combinations of steroidal alkaloids and conessine with antibiotics was compared with antibiotic treatment alone via MIC determination and time-kill assays. Efficacy of combinations of the steroidal alkaloids and conessine with levofloxacin were compared with monotherapies against infections in G. mellonella larvae by measuring larval mortality and bacterial burden. Results: Combination therapies of conessine or steroidal alkaloids with levofloxacin enhanced bacterial inhibition in vitro and restored antibiotic efficacy in vivo compared to the constituent monotherapies. Neither conessine nor the steroidal alkaloids induced any detectable toxicity in G. mellonella larvae. The enhanced efficacy of the combination treatments was most pronounced with conessine and correlated with reduced larval burden of infecting P. aeruginosa. Notably, the enhanced efficacy of conessine/levofloxacin combinations was only detected in the parent strain and strains that overexpressed the MexAB-OprM or MexEF-OprN efflux systems. Conclusions: Steroidal alkaloids from Holarrhena antidysenterica, and particularly the principal active ingredient conessine, restored levofloxacin efficacy against resistant P. aeruginosa strains possessing efflux-mediated MDR phenotypes. The compounds should be investigated further as a potential novel therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
12. John Stenhouse: Contribution to the study of active charcoal, lichens, and alkaloids.
- Author
-
Wisniak, Jaime
- Subjects
- *
LICHENS , *ALKALOIDS , *ACTIVATED carbon , *ASTRINGENTS , *GAS masks , *ADSORPTION (Chemistry) , *ORCIN - Abstract
John Stenhouse (1809-1880) carried a large number of experiments comparing the adsorbing power of wood and animal charcoal for the gases ammonia, hydrogen sulfide, sulfur dioxide, and carbon dioxide, as well as their decolorizing and oxidation ability. The results led him to suggest that charcoal could be used to absorb the small amount of infectious matter floating in the atmosphere of unhealthy locations (as was the belief in those days). Consequently, he designed a charcoal air filter consisting of a thin layer of charcoal powder enclosed between two sheets of wire gauze, as well as personal respirators to be used over the mouth or nostrils and mouth. Stenhouse also studied the dyes present in lichens, particularly in the varieties of Orchella weed Rocella tinctoria, Rocella Montagnei, Gyrophora pustulata, and Lecanora tartarea. He described the extraction, purification and analytical procedures of the different dyes and discovered a series of intermediate compounds, among them, alpha and beta orsellic acids, roccellinin acid, erythreselic and usnic acid, pico-erythricin, pseudo-orcin (erythromannitol), erythromannitol pentanitrate (an explosive), betorcinol (a homolog of orcinol). Stenhouse proved that it was possible to obtain, artificial alkaloids using as starting materials the highly nitrogenated compound principles (i.e. albumen, fibrin, legumin, etc.) found in all plants, known to be as rich in nitrogen as the corresponding animal compounds. He also developed an analytical procedure for detecting quinic acid, discovered the presence of sparteine in a variety of vegetables and the active principle connesine (wrightine) in the seeds of the tree Wrightia antidysenterica. [ABSTRACT FROM AUTHOR]
- Published
- 2018
13. Atomistic insight and modeled elucidation of conessine towards Pseudomonas aeruginosa efflux pump
- Author
-
Varomyalin Tipmanee, Supayang Piyawan Voravuthikunchai, Thanyaluck Siriyong, Thanyada Rungrotmongkol, Dennapa Saeloh, Juntamanee Jewboonchu, and Jirakrit Saetang
- Subjects
0303 health sciences ,biology ,Pseudomonas aeruginosa ,030303 biophysics ,General Medicine ,medicine.disease_cause ,biology.organism_classification ,03 medical and health sciences ,Conessine ,chemistry.chemical_compound ,chemistry ,Structural Biology ,Glycine ,Biophysics ,medicine ,Efflux ,Binding site ,Mode of action ,Lipid bilayer ,Molecular Biology ,Holarrhena - Abstract
Drug-resistant Pseudomonas aeruginosa efflux pump extrudes antibiotics from cells for survival. Efflux pump inhibitor (EPI) thus becomes an interesting alternative to handle the drug-resistant bacteria. Conessine, a natural steroidal alkaloid from Holarrhena antidysenterica, previously exhibited efflux pump inhibitory potential. Our molecular docking and molecular dynamics (MD) studies provided atomistic information as well as the interaction of conessine with bacterial MexB efflux pump in phospholipid bilayer membrane to further the previous experimental report. Herein, the binding site and proposed mode of action of conessine were identified compared to known/commercial EPIs such as PAβN or designed-synthetic P9D. Our results explained conessine binding mode of action as an effective agent against the MexB efflux pump. The MD simulation also suggested that conessine was able to affect glycine loop (G-loop) flexibility, and the reduced G-loop flexibility due to conessine could hinder an antibiotics extrusion. In addition, our study suggested the conessine core structure buried in a hydrophobic region in the efflux pump similar to other known EPIs. Our finding could cope as a key for the design and development of the conessine derivative as novel EPI against P. aeruginosa.Communicated by Ramaswamy H. Sarma.
- Published
- 2020
14. Determination of Histamine H3-Receptor Antagonist Conessine in Wistar Rat Plasma by a Rapid and Sensitive RP-UFLC Method: Application to a Pharmacokinetic Study
- Author
-
Shubhashri Mohire, K. Elango, Mahesh Thondawada, Karthik Yamjala, Vishakantha Murthy, Nilesh Sudhakar Ambhore, Shashank Mulukutla, and Rama Satyanarayana Raju Kalidhindi
- Subjects
chemistry.chemical_compound ,Conessine ,Chromatography ,chemistry ,Pharmacokinetics ,Antagonist ,Protein precipitation ,Absorption (skin) ,General Pharmacology, Toxicology and Pharmaceutics ,Histamine H3 receptor ,Histamine ,Bioavailability - Abstract
Objectives: Epidemiological data suggests the highest density of histamine H3-receptors (H3R) in basal ganglia of central nervous system (CNS) wherein they function as inhibitory auto-receptors and control the release of many neurotransmitters. Inhibition of H3R increases the turnover of neurotransmitters, especially dopamine in basal ganglia and could be beneficial to treat Parkinson’s disease. Methods: In this study, we formulated the brain targeting liposomes of conessine, a selective antagonist for H3R to increase bioavailability and developed and validated a rapid and sensitive reverse phase ultra-force liquid chromatographic (RP-UFLC) method and to quantitate conessine in Wistar rat plasma and tissue. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and aripiprazole as the internal standard. Chromatographic separation was performed on the Hibar C18 column with a mobile phase of Hexane Sulphonic acid (10 mM, pH 10.0 adjusted with ammonia) and methanol at a flow rate of 0.9 ml/min. Results: The lower limit of quantification of the developed method was 4.0 ng/ml and 6.0 ng/g in plasma and tissue samples, respectively. Liposomes of conessine (equivalent to 20 mg/kg) administered orally to animals, demonstrated remarkable absorption into the systemic circulation with maximum concentration (~8700 ng/ ml) within 2.0 h. The order of area under curve was found to be kidney> brain> liver> lungs> spleen> heart. Conclusion: The liposomes of conessine were rapidly taken up into the brain and showed a good brain concentration after 2.0 h; sustenance up to 4.0 h was achieved which is better than conessine solution. Key words: Conessine, RP-UFLC method, Pharmacokinetic, Tissue distribution, Validation.
- Published
- 2020
15. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice.
- Author
-
Morais-Silva, Gessynger, Ferreira-Santos, Mariane, and Marin, Marcelo T.
- Subjects
- *
NEUROCHEMISTRY , *ETHANOL , *PHYSIOLOGICAL effects of alcohol , *NEUROTRANSMITTERS , *LABORATORY mice , *PHYSIOLOGICAL effects of alkaloids , *HISTAMINE receptors , *PHYSIOLOGY - Abstract
Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H 3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H 3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H 3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H 3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
16. Molecular dynamics simulation analysis of conessine against multi drug resistant Serratia marcescens
- Author
-
Pramod Kumar Yadav, Kalyani Dhusia, Pramod W. Ramteke, Kalpana Raja, Pierre P. M. Thomas, RS: GROW - R4 - Reproductive and Perinatal Medicine, Institute for Public Health Genomics, and Genetica & Celbiologie
- Subjects
0301 basic medicine ,Serratia ,genetic structures ,PREDICTION ,ORNITHINE-DECARBOXYLASE ,Drug Evaluation, Preclinical ,Molecular Conformation ,EFFICIENT ,PROTEIN ,Quantitative Structure-Activity Relationship ,Ligands ,Ornithine decarboxylase ,chemistry.chemical_compound ,Catalytic Domain ,Drug Resistance, Multiple, Bacterial ,Protein Interaction Mapping ,DOCKING ,Protein Interaction Maps ,Serratia marcescens ,chemistry.chemical_classification ,biology ,Ligand (biochemistry) ,PUTRESCINE ,Anti-Bacterial Agents ,Infectious Diseases ,INFECTIONS ,ACID ,Protein Binding ,Microbiology (medical) ,Stereochemistry ,030106 microbiology ,Molecular Dynamics Simulation ,Microbiology ,03 medical and health sciences ,Alkaloids ,Bacterial Proteins ,Ornithine de carboxylase ,Genetics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Binding Sites ,fungi ,Hydrogen Bonding ,biology.organism_classification ,Nosocomial diseases ,PREVENTION ,POLYAMINES ,Conessine ,030104 developmental biology ,Enzyme ,chemistry ,Docking (molecular) ,INHIBITORS ,Holarrhena - Abstract
Ornithine decarboxylase (ODC) is an immediate precursor of polyamine biosynthesis in Serratia marcescens and a potential target for inhibition of its growth. We predicted the 3D structural conformation of ODC enzyme and validated it using MDS in our previous study. In this current study, the potential inhibitors of ODC were obtained by virtual screening of potential inhibitors from ZINC database and studied in depth for their different binding pose. Among the ten virtually screened inhibitors, Conessine exhibited the best binding with ODC and its inhibition property was studied further by MDS studies. The natural compound conessine is isolated from plant Holarrhena antidysenterica and it is studied against ODC of Serratia marcenses for its inhibitory potentials. This revealed unforeseen twisted position in root mean square fluctuation (RMSF) and ODC modelled conformation that influenced ligand binding. Both predicted model and ligand bound model were compared and found to be stable with Root Mean Square Deviation (RMSD) of approximately 7 nm and 0.25 nm to that of crystallographic structure over simulation time of 55 ns and 70 ns respectively. This work paves the way for future development of new drugs against nosocomial diseases caused by Serratia marcescens.
- Published
- 2019
17. Metabolic Diversity and Therapeutic Potential of Holarrhena pubescens: An Important Ethnomedicinal Plant
- Author
-
Sujogya Kumar Panda, Shasank S. Swain, Kulsoom Zahara, and Walter Luyten
- Subjects
Gastrointestinal Diseases ,lcsh:QR1-502 ,Review ,STEROIDAL ALKALOIDS ,Biochemistry ,lcsh:Microbiology ,Holarrhena pubescens ,chemistry.chemical_compound ,0302 clinical medicine ,ETHNOPHARMACOLOGICAL SURVEY ,ethnopharmacology ,phytoconstituents ,Holarrhena ,0303 health sciences ,Traditional medicine ,Apocynaceae ,biology ,Biodiversity ,Indian subcontinent ,Phytochemical ,030220 oncology & carcinogenesis ,ETHNOBOTANICAL SURVEY ,TRADITIONAL HEALERS ,SHIMOGA DISTRICT ,Life Sciences & Biomedicine ,pharmacokinetics ,Biochemistry & Molecular Biology ,MEDICO-BOTANICAL KNOWLEDGE ,Critical discussion ,Metabolic diversity ,03 medical and health sciences ,Phytochemical composition ,Diabetes Mellitus ,Humans ,HEALTH-CARE PRACTICES ,Molecular Biology ,030304 developmental biology ,Science & Technology ,Plants, Medicinal ,Plant Extracts ,toxicity ,biology.organism_classification ,Medicine, Ayurvedic ,Conessine ,UTTARA-KANNADA DISTRICT ,chemistry ,bioactivity ,MAYURBHANJ DISTRICT ,Medicine, Traditional ,ANTIDYSENTERICA EXTRACT ,Phytotherapy - Abstract
Holarrhena pubescens is an important medicinal plant of the Apocynaceae family that is widely distributed over the Indian subcontinent. The plant is extensively used in Ayurveda and other traditional medicinal systems without obvious adverse effects. Beside notable progress in the biological and phytochemical evaluation of this plant over the past few years, comprehensive reviews of H. pubescens are limited in scope. It has economic importance due to the extensive use of seeds as an antidiabetic. Furthermore, the plant is extensively reported in traditional uses among the natives of Asia and Africa, while scientifical validation for various ailments has not been studied either in vitro or in vivo. This review aims to summarize information on the pharmacology, traditional uses, active constituents, safety and toxicity of H. pubescens. Chemical analysis of H. pubescens extracts revealed the presence of several bioactive compounds, such as conessine, isoconnessine, conessimine, conimine, conessidine, conkurchicine, holarrhimine, conarrhimine, mokluangin A-D and antidysentericine. Overall, this review covers the ethnopharmacology, phytochemical composition, and pharmacological potential of H. pubescens, with a critical discussion of its toxicity, biological activities (in vitro and in vivo), the mechanism of action, as well as suggestions for further basic and clinical research. ispartof: BIOMOLECULES vol:10 issue:9 ispartof: location:Switzerland status: published
- Published
- 2020
18. Indigenous Medicinal Plants as Biofilm Inhibitors for the Mitigation of Antimicrobial Resistance
- Author
-
Evelyn Asante-Kwatia, Isaac Kingsley Amponsah, Philip Kobla Atchoglo, Elikplim Kwesi Ampofo, Francis Ackah Armah, and Abraham Yeboah Mensah
- Subjects
0301 basic medicine ,Article Subject ,030106 microbiology ,RM1-950 ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,medicine ,Pharmacology (medical) ,Petroleum ether ,General Pharmacology, Toxicology and Pharmaceutics ,Medicinal plants ,biology ,Traditional medicine ,Organic Chemistry ,Biofilm ,Pathogenic bacteria ,biology.organism_classification ,Antimicrobial ,Conessine ,030104 developmental biology ,chemistry ,Therapeutics. Pharmacology ,Antibacterial activity ,Research Article ,Holarrhena - Abstract
The majority of indigenes in the rural areas of Ghana use herbal medicines for their primary health care. In this study, an ethnobotanical survey was undertaken to document medicinal plants used by traditional healers in the Ejisu-Juaben district in the Ashanti region of Ghana to treat infections and to further investigate the antibiofilm formation properties of selected plants in resisting pathogenic bacteria. Seventy medicinal plants used by traditional practitioners for the treatment of skin infections and wounds were documented from the ethnobotanical survey. Forty out of the seventy plants were collected and their methanol extracts evaluated for antimicrobial activity by the agar diffusion assay. Extracts that showed antibacterial activity were tested for biofilm inhibitory activity, and the most active plant was subsequently purified to obtain the active constituents. Biofilm formation was significantly mitigated by petroleum ether, ethyl acetate, and methanol extracts of Holarrhena floribunda stem bark. Bioassay-guided fractionation of an alkaloidal extract prepared from the methanol fraction led to the isolation of three steroidal alkaloids, namely, holonamine, holadienine, and conessine. The isolated compounds demonstrated varying degrees of biofilm formation inhibitory properties. The current study reveals that screening of indigenous medicinal plants could unravel potential leads to salvage the declining efficacy of conventional antibiotics. Holarrhena floribunda stem bark extract has strong biofilm formation inhibition properties, which could be attributed to the presence of steroidal alkaloids.
- Published
- 2020
- Full Text
- View/download PDF
19. Holarrhena pubescens Wall. ex G. Don. (Apocynaceae)
- Author
-
Shahid Akbar
- Subjects
Holarrhena pubescens ,biology ,Traditional medicine ,Astringent ,business.industry ,Phlegm ,Dysentery ,Decoction ,medicine.disease ,biology.organism_classification ,complex mixtures ,Conessine ,chemistry.chemical_compound ,chemistry ,visual_art ,medicine ,visual_art.visual_art_medium ,Bark ,medicine.symptom ,business ,Stomachic - Abstract
It is native to central and southern Africa, the Indian subcontinent, Indochina, and parts of China. Bark is bitter, stomachic, astringent, powerful antidysenteric, febrifuge and anthelmintic, and constitutes the principal medicine for dysentery in all systems of traditional Indian medicine. The bark is one of the most important drugs in Hindu Materia Medica, and is described as astringent, cold and digestive, and is a remedy for piles, dysentery, leprosy and phlegmatic humours. Sushruta said it is expectorant, an antidote to poisons, cures dysuria, urinary and skin diseases, checks nausea and vomiting, allays pruritus, improves the condition of bad ulcers, relieves stomach pain and checks the derangement of three humours, i.e. phlegm, air and bile. According to Charaka and Sushruta, every part of the plant except the flower is used as a snakebite remedy; certain authors have disputed this property. Seeds are cooling, appetizer, astringent, anthelmintic, analgesic and used for leprosy, burning sensations, dysentery, skin diseases, biliousness, bleeding piles, fatigue and hallucinations. In Portugese traditional medicine, the bark is used as plaster in rheumatism, hot decoction is used against toothache and bowel affections and the root-bark is used in chronic fevers. Kurchi contains numerous steroidal alkaloids, including norconessine, isoconessine, and kurchine. Conessine hydrobromide is obtained from seeds. Alkaloidal contents seasonally vary in different parts, and in the bark during different stages. Steroidal alkaloids, conessine, conessimine, conarrhimin and conimine show strong AChE inhibitory activity, conessimine being the strongest. In a clinical trial of 40 Indian patients with 15 patients stool positive for E. histolytica cysts, 20 for G. lamblia and five for both, the bark powder for 15-days significantly improved symptoms and stools negative for E. histolytica cyst in 70% cases.
- Published
- 2020
20. Crystallographic analysis and structural conformational study of conessine: A steroidal alkaloid
- Author
-
Naresh Sharma, Vivek Kumar Gupta, Dwijendra K. Gupta, and Rakesh Sharma
- Subjects
Diffraction ,Conessine ,chemistry.chemical_compound ,Crystallography ,Materials science ,chemistry ,Direct method ,Steroidal alkaloid ,Orthorhombic crystal system ,Crystal structure ,Single crystal - Abstract
The compound crystallizes in the orthorhombic crystal system with space group P212121 having unit cell parameters: a=10.840(13), b=10.896(6), c=18.903(6) A and Z=4. The crystal structure was solved by direct method using single crystal X-ray diffraction data collected at room temperature and refined by full-matrix least-squares procedures to a final R-value of 0.062 for 1044 observed reflections.
- Published
- 2020
21. In vitro elicitation, isolation, and characterization of conessine biomolecule from Holarrhena antidysenterica (L.) Wall. callus and its larvicidal activity against malaria vector, Anopheles stephensi Liston
- Author
-
Dinesh Kumar, Ram Das, Gaurav Kumar, Ravindra Kumar, and Veena Agrawal
- Subjects
0106 biological sciences ,0301 basic medicine ,Insecticides ,Health, Toxicology and Mutagenesis ,Phenylalanine ,Insect Control ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,Murashige and Skoog medium ,Anopheles ,Animals ,Environmental Chemistry ,Yeast extract ,Anopheles stephensi ,Holarrhena ,Chromatography ,biology ,Chemistry ,food and beverages ,General Medicine ,biology.organism_classification ,Pollution ,Elicitor ,Conessine ,030104 developmental biology ,Larva ,Callus ,010606 plant biology & botany - Abstract
In vitro elicitation of an important compound conessine has been done in the bark-derived callus culture of Holarrhena antidysenterica (L.) Wall. employing different elicitors. For induction of callus, green bark explants excised from field-grown plants were cultured on MS medium augmented with different concentrations (0, 1, 2.5, 5, and 10 μM) of various growth regulators such as BA, IBA, NAA, and 2,4-D either alone or in combinations. The maximum amount of conessine (458.18 ± 0.89d μg/g dry wt.) was achieved in callus developed on MS medium supplemented with 5 μM BA and 5 μM 2,4-D through HPLC analysis. Elicitation in conessine content in the above callus was achieved employing a variety of organic (phenylalanine, tyrosine, chitosan, tryptophan, casein hydrolysate, proline, sucrose, and yeast extract) as well as inorganic elicitors (Pb(NO3)2, As2O3, CuSO4, NaCl, and CdCl2) in different concentrations. The optimum enhancement in conessine content (3518.58 ± 0.28g μg/g dry wt.) was seen at the highest concentration (200 mg/L) of phenylalanine. The enhancement was elicitor specific and dose dependent. The overall increment of the conessine content was seen in the order of phenylalanine > tryptophan > Pb(NO3)2 > sucrose > NaCl > As2O3 > casein hydrolysate > CdCl2 > chitosan > proline > yeast extract > CuSO4 > tyrosine. The isolation and purification of conessine was done using methanol as a solvent system through column chromatography (CC) and TLC. The isolated compound was characterized by FT-IR, 1H-NMR, and HRMS which confirmed with the structure of conessine. The bioassays conducted with the isolated compound revealed a strong larvicidal activity against Anopheles stephensi Liston with LC50 and LC90 values being 1.93 and 5.67 ppm, respectively, without harming the nontarget organism, Mesocyclops thermocyclopoides Harada, after 48 h of treatment. This is our first report for the isolation and elicitation of conessine in the callus culture of H. antidysenterica.
- Published
- 2017
22. Antimicrobial activity of the methanolic bark extract of Holarrhena pubescens (Buch. Ham), its fractions and the pure compound conessine.
- Author
-
Siddiqui, BinaS., Ali, SyedTahir, Rizwani, GhazalaH., Begum, Sabira, Tauseef, Saima, and Ahmad, Aqeel
- Abstract
The antimicrobial activity of the methanolic extract of the bark of Holarrhena pubescens, its fractions, and conessine, a steroidal alkaloid, was determined against various bacteria and fungi using the agar diffusion method. They were all found to possess significant activity against some of the bacteria tested. The alkaloidal fraction and conessine also exhibited marginal activity against some of the fungi tested. The minimum inhibitory concentration (MIC) value of conessine was determined against various bacteria, and the highest activity was seen against Micrococcus luteus ATCC 9341 (MIC: 15.6 µg per disc). [ABSTRACT FROM PUBLISHER]
- Published
- 2012
- Full Text
- View/download PDF
23. Chromatographic Analysis of Bioactive Markers in Vidangarista, an Ayurvedic Polyherbal Formulation.
- Author
-
Bhujbal, Pallavi S. and Sandhya, Parameswaran
- Abstract
Vidangarista is an ayurvedic polyherbal formulation officially recorded in the Ayurvedic formulary of India and used as an anthelmintic. The herbal formulation contains many plant constituents, and hence a large number of markers should be quantified to assess its quality. This paper reports the standardization of Vidangarista by HPTLC analysis for the presence of the biomarkers gallic acid and conessine. Each marker compound showed a linear relationship with an average r² = 0.99 in the concentration range studied. The proposed method was found to be precise, specific, and accurate, with a recovery of 99-101%, and hence can be used for routine analysis of this formulation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
24. Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic
- Author
-
Aamer Saeed, Reem Ghonaim, Nermeen Yosri, Haged H R El-Seedi, Hesham R. El-Seedi, Chao Zhao, Syed Ghulam Musharraf, Jianbo Xiao, Zhiming Guo, Shaden A. M. Khalifa, Alfi Khatib, Mohamed F. El-Mallah, Ming Du, and Thomas Efferth
- Subjects
COVID-19 Vaccines ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Antiviral Agents ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Clinical trials ,0302 clinical medicine ,Tocilizumab ,Chloroquine ,Drug Discovery ,Pandemic ,medicine ,Humans ,Antiviral ,Pandemics ,030304 developmental biology ,Pharmacology ,Biological Products ,Clinical Trials as Topic ,Natural products ,0303 health sciences ,Protection ,Molecular Structure ,Traditional medicine ,SARS-CoV-2 ,business.industry ,COVID-19 ,Lycorine ,Fingolimod ,COVID-19 Drug Treatment ,Clinical trial ,Conessine ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Molecular Medicine ,Patent ,Plant Preparations ,business ,medicine.drug - Abstract
Background Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge. Methods A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar). Results Through the screening for natural products with antiviral activities against seven types of the human coronavirus, extracts of Lycoris radiata, Gentiana scabra, Dioscorea batatas, Cassia tora, Taxillus chinensis Cibotium barometz and Echinacea purpurea showed a promising effect against SARS-COV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab. Conclusion Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19., Graphical Abstract Image, graphical abstract
- Published
- 2021
25. A new family of H3 receptor antagonists based on the natural product Conessine
- Author
-
Santora, Vincent J., Covel, Jonathan A., Hayashi, Rena, Hofilena, Brian J., Ibarra, Jason B., Pulley, Michelle D., Weinhouse, Michael I., Sengupta, Dipanjan, Duffield, Jonathan J., Semple, Graeme, Webb, Robert R., Sage, Carleton, Ren, Albert, Pereira, Guilherme, Knudsen, Jens, Edwards, Jeffrey E., Suarez, Marissa, Frazer, John, Thomsen, William, and Hauser, Erin
- Subjects
- *
INFLAMMATORY mediators , *ANTIHISTAMINES , *HISTAMINE , *IMIDAZOLES - Abstract
Abstract: A new family of Histamine H3 receptor antagonists (5a–t) has been prepared based on the structure of the natural product Conessine, a known H3 antagonist. Several members of the new series are highly potent and selective binders of rat and human H3 receptors and display inverse agonism at the human H3 receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H3 receptor in an in-vivo pharmacological model. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
26. High-performance thin layer chromatography method for estimation of conessine in herbal extract and pharmaceutical dosage formulations
- Author
-
Kaur, Aman D., Ravichandran, V., Jain, Prateek K., and Agrawal, Ram K.
- Subjects
- *
CHROMATOGRAPHIC analysis , *DOSAGE forms of drugs , *COLLOIDS , *DRUG delivery systems - Abstract
Abstract: A new, simple, sensitive, precise and robust high-performance thin layer chromatographic (HPTLC) method was developed for the estimation of conessine in herbal extracts and pharmaceutical dosage forms. Analysis of conessine was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of toluene–ethylacetate–diethyl amine (6.5:2.5:1, v/v/v) at room temperature (25±2°C). After derivatized the plate with modified Dragendroff''s reagent, Camag TLC scanner III was used for spectrodensitometric scanning and analysis of the plate in absorbance mode at 520nm. The system was found to give compact spots for conessine (R f value of 0.82). The data for calibration plots showed good linear relationship with r 2 =0.9998 in the concentration range of 1–10μg with respect to peak area. The present method was validated for precision and recovery. The limits of detection and quantification were determined. Statistical analysis of the data showed that the method is reproducible and selective for estimation of conessine. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
27. Antibacterial steroidal alkaloids from Holarrhena antidysenteriaca
- Author
-
Xiao-Lei Ge, Ting-Ting Dong, Bo-Hang Sun, Hui-Yuan Gao, and Li-Na Zhou
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Staphylococcus aureus ,030232 urology & nephrology ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,0302 clinical medicine ,Drug Discovery ,medicine ,Methicillin sensitive ,Holarrhena ,biology ,Plant Extracts ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Penicillin ,Conessine ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Vancomycin ,Antibacterial activity ,medicine.drug - Abstract
Two new steroidal alkaloids, isoconkuressine and N-formylconessimine, together with 6 known steroidal alkaloids including conkuressine, conessine, isoconessimine, conimine, conarrhimine, and funtudienine, were isolated from the seeds of Holarrhena antidysenteriaca Wall.ex A.DC. Their intrinsic antibacterial activities and synergistic effects with penicillin and vancomycin were analyzed in methicillin sensitive staphylococcus aureus (MSSA) and methicillin resistant staphylococcus aureus (MRSA). Two of the steroidal alkaloids including one new compound (N-formylconessimine) showed potential antibacterial activity and possessed synergistic effects with penicillin and vancomycin, respectively.
- Published
- 2017
28. Influence of Demographic Location and Solvent Extraction on Pharmacognostical Assessment and Identification of Conessine Content in Different Parts of Holarrhena antidysentrica Through HPTLC Analysis
- Author
-
Kuntal Das and Raman Dang
- Subjects
0106 biological sciences ,Chromatography ,biology ,biology.organism_classification ,030226 pharmacology & pharmacy ,01 natural sciences ,03 medical and health sciences ,Conessine ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,010608 biotechnology ,Identification (biology) ,General Pharmacology, Toxicology and Pharmaceutics ,Solvent extraction ,Holarrhena - Published
- 2017
29. Atomistic insight and modeled elucidation of conessine towards Pseudomonas aeruginosa efflux pump.
- Author
-
Jewboonchu J, Saetang J, Saeloh D, Siriyong T, Rungrotmongkol T, Voravuthikunchai SP, and Tipmanee V
- Subjects
- Anti-Bacterial Agents metabolism, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Molecular Docking Simulation, Alkaloids pharmacology, Pseudomonas aeruginosa
- Abstract
Drug-resistant Pseudomonas aeruginosa efflux pump extrudes antibiotics from cells for survival. Efflux pump inhibitor (EPI) thus becomes an interesting alternative to handle the drug-resistant bacteria. Conessine, a natural steroidal alkaloid from Holarrhena antidysenterica , previously exhibited efflux pump inhibitory potential. Our molecular docking and molecular dynamics (MD) studies provided atomistic information as well as the interaction of conessine with bacterial MexB efflux pump in phospholipid bilayer membrane to further the previous experimental report. Herein, the binding site and proposed mode of action of conessine were identified compared to known/commercial EPIs such as PAβN or designed-synthetic P9D. Our results explained conessine binding mode of action as an effective agent against the MexB efflux pump. The MD simulation also suggested that conessine was able to affect glycine loop (G-loop) flexibility, and the reduced G-loop flexibility due to conessine could hinder an antibiotics extrusion. In addition, our study suggested the conessine core structure buried in a hydrophobic region in the efflux pump similar to other known EPIs. Our finding could cope as a key for the design and development of the conessine derivative as novel EPI against P. aeruginosa .Communicated by Ramaswamy H. Sarma.
- Published
- 2022
- Full Text
- View/download PDF
30. Corrosion Inhibition of Mild Steel in 0.5 M H2SO4 Using Ethanol Extract of Funtumia elastica
- Author
-
Emeka E. Oguzie, Chinonso Blessing Adindu, and Cynthia E. Ogukwe
- Subjects
biology ,Chemistry ,Inorganic chemistry ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Ascorbic acid ,Electrochemistry ,01 natural sciences ,0104 chemical sciences ,Corrosion ,Conessine ,chemistry.chemical_compound ,Corrosion inhibitor ,Funtumia elastica ,Gravimetric analysis ,Fourier transform infrared spectroscopy ,0210 nano-technology - Abstract
The adsorption and corrosion inhibitive effect of the ethanol extract of Funtumia elastica (FE) leaves on mild steel corrosion in 0.5 M H2SO4 was studied using gravimetric, potentiodynamic polarization and electrochemical impedance spectroscopic techniques. As well as Fourier transform infrared spectroscopy and computational methods. The gravimetric and electrochemical studies revealed that FE is an adsorption inhibitor. The potentiodynamic polarization result showed that the inhibitor is a mixed type corrosion inhibitor for mild steel in 0.5 M H2SO4, inhibiting both the cathodic and anodic partial reactions. Density functional theory calculations were performed to model the electronic structures of some selected extract constituents (conessine, and ascorbic acid) to confirm their inhibiting potential and established their individual contributions to the observed inhibiting effects.
- Published
- 2016
31. Holarrhena antidysenterica Extract and Its Steroidal Alkaloid, Conessine, as Resistance-Modifying Agents Against Extensively Drug-Resistant Acinetobacter baumannii
- Author
-
Varomyalin Tipmanee, Potjanee Srimanote, Supayang Piyawan Voravuthikunchai, Sasitorn Chusri, and Thanyaluck Siriyong
- Subjects
Acinetobacter baumannii ,0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Immunology ,Microbial Sensitivity Tests ,Drug resistance ,Pharmacology ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,Drug Resistance, Multiple, Bacterial ,Ethidium ,medicine ,Humans ,Pyronine ,Novobiocin ,Holarrhena ,biology ,Plant Extracts ,Biological Transport ,Drug Synergism ,biology.organism_classification ,Anti-Bacterial Agents ,Conessine ,1-Naphthylamine ,030104 developmental biology ,chemistry ,Drug Therapy, Combination ,Efflux ,Rifampin ,Ethidium bromide ,Rifampicin ,medicine.drug - Abstract
Emergence and spread of antibiotic-resistant Acinetobacter baumannii have become a major public health concern. This study was designed to investigate the efficacy of Holarrhena antidysenterica extract and its major steroidal alkaloid conessine as resistance-modifying agents (RMAs) on the susceptibility of A. baumannii to novobiocin and rifampicin. A significant synergistic activity of both the extract and conessine in combination with either novobiocin or rifampicin with fractional inhibitory concentration index ≤0.5 was demonstrated. Fluorescent dyes and different efflux pump inhibitors were used to further investigate the synergism. Increase in the uptake of 1-N-phenylnaphthylamine in the bacterial cells treated with the extract and conessine was not observed indicating that both substances did not act as permeabilizers. With regard to efflux pump inhibition, no accumulation in ethidium bromide (EtBr) was noticed suggesting that the AdeABC pump was not involved. In contrast, accumulation in Pyronin Y was significantly increased (p 0.05) demonstrating that the synergism was due to interference with the AdeIJK pump. Study on frequencies of the spontaneous mutational resistance to the extract in combination with antibiotics demonstrated attenuation in drug-resistant organisms. Thus, H. antidysenterica extract and conessine as RMAs may offer a combinatory therapy to restore antibiotic susceptibility in the extensively drug-resistant A. baumannii.
- Published
- 2016
32. Neuroprotective effect of Conessinin on Elevated oxidative stress induced Alzheimers'disease in rats
- Author
-
Nagaraju Bandaru, A. Ankarao, Uma Sankar Gorla, Chandrasekhar Komavari, Gsn Koteswarao, and Umasankar Kulandaivelu
- Subjects
business.industry ,medicine.drug_class ,Disease ,Anti oxidant ,Pharmacology ,Malondialdehyde ,medicine.disease ,medicine.disease_cause ,Neuroprotection ,Anti-inflammatory ,chemistry.chemical_compound ,Conessine ,chemistry ,medicine ,Pharmacology (medical) ,Alzheimer's disease ,business ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Oxidative stress - Published
- 2020
33. Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection
- Author
-
Thanyaluck, Siriyong, Supayang Piyawan, Voravuthikunchai, Peter John, Coote, University of St Andrews. Biomedical Sciences Research Complex, and University of St Andrews. School of Biology
- Subjects
ATP Binding Cassette Transporter, Subfamily B ,Colony Count, Microbial ,RV ,Moths ,Alkaloids ,Bacterial Proteins ,Drug Resistance, Multiple, Bacterial ,Mex efflux systems ,Animals ,Pseudomonas Infections ,heterocyclic compounds ,RV Botanic, Thomsonian, and eclectic medicine ,Holarrhena ,Holarrhena antidysenterica ,Conessine ,fungi ,DAS ,lcsh:Other systems of medicine ,biochemical phenomena, metabolism, and nutrition ,lcsh:RZ201-999 ,Anti-Bacterial Agents ,Disease Models, Animal ,Galleria mellonella ,Pseudomonas aeruginosa ,Efflux pump inhibitor ,Research Article - Abstract
This work was supported by the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0041/2556) co-funded by the Newton Fund of the British Council and TRF Senior Research Scholar (Grant No. RTA 5880005). Background This study aimed to evaluate the efficacy of combinations of steroidal alkaloids and conessine from the Thai medicinal plant Holarrhena antidysenterica with antibiotics against Pseudomonas aeruginosa strains possessing different efflux-pump-mediated multidrug-resistant (MDR) phenotypes in a Galleria mellonella infection model. Methods P. aeruginosa strains with defined mutations that result in the overexpression of the MexAB-OprM, MexCD-OprJ and MexEF-OprN efflux pumps, and a strain with all three of these pumps deleted, were used. In vitro, the effect of combinations of steroidal alkaloids and conessine with antibiotics was compared with antibiotic treatment alone via MIC determination and time-kill assays. Efficacy of combinations of the steroidal alkaloids and conessine with levofloxacin were compared with monotherapies against infections in G. mellonella larvae by measuring larval mortality and bacterial burden. Results Combination therapies of conessine or steroidal alkaloids with levofloxacin enhanced bacterial inhibition in vitro and restored antibiotic efficacy in vivo compared to the constituent monotherapies. Neither conessine nor the steroidal alkaloids induced any detectable toxicity in G. mellonella larvae. The enhanced efficacy of the combination treatments was most pronounced with conessine and correlated with reduced larval burden of infecting P. aeruginosa. Notably, the enhanced efficacy of conessine/levofloxacin combinations was only detected in the parent strain and strains that overexpressed the MexAB-OprM or MexEF-OprN efflux systems. Conclusions Steroidal alkaloids from Holarrhena antidysenterica, and particularly the principal active ingredient conessine, restored levofloxacin efficacy against resistant P. aeruginosa strains possessing efflux-mediated MDR phenotypes. The compounds should be investigated further as a potential novel therapy. Publisher PDF
- Published
- 2018
34. Conessine treatment reduces dexamethasone-induced muscle atrophy by regulating MuRF1 and atrogin-1 expression
- Author
-
Won Keun Oh, Rackhyun Park, Daum Jo, Junsoo Park, Inho Choi, Joonho Choe, Hyun-Ju Kim, and Minsu Jang
- Subjects
0301 basic medicine ,Programmed cell death ,Cell signaling ,Ubiquitin-Protein Ligases ,Muscle Proteins ,Pharmacology ,Applied Microbiology and Biotechnology ,Dexamethasone ,Cell Line ,Tripartite Motif Proteins ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,Western blot ,Ubiquitin ,medicine ,Animals ,Humans ,RNA, Messenger ,Muscle, Skeletal ,SKP Cullin F-Box Protein Ligases ,medicine.diagnostic_test ,biology ,Forkhead Box Protein O3 ,Autophagy ,NF-kappa B ,General Medicine ,Muscle atrophy ,Muscular Atrophy ,Conessine ,HEK293 Cells ,030104 developmental biology ,chemistry ,Protein Biosynthesis ,biology.protein ,medicine.symptom ,C2C12 ,Signal Transduction ,Biotechnology - Abstract
Conessine, a steroidal alkaloid, is a potent histamine H3 antagonist with anti-malarial activity. We recently reported that conessine treatment interferes with H₂O₂-induced cell death by regulating autophagy. However, the cellular signaling pathways involved in conessine treatment are not fully understood. Here, we report that conessine reduces muscle atrophy by interfering with the expression of atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Promoter reporter assay revealed that conessine treatment inhibits FoxO3a-dependent transcription, NF-kappaB-dependent transcription and p53-dependent transcription. We also showed that conessine treatment reduced dexamethasone-induced expression of MuRF1 and atrogin-1 by the quantitative RT-PCR and Western blot. Finally, we demonstrated that conessine treatment reduced dexamethasone-induced muscle atrophy using differentiated C2C12 cells. These results collectively suggest that conessine is potentially useful in the treatment of muscle atrophy.
- Published
- 2017
35. Comparison of anti amoebic activity of stereoisomeric diamino and monoamino pregnene alkaloids and their N-methylated analogs.
- Author
-
VAID, RAJ and BHUTANI, K
- Subjects
- *
AMEBIASIS , *STEREOISOMERS , *AMINO acids , *ALKALOIDS , *METHYLATION , *COMPARATIVE studies , *STEROIDS - Abstract
The steroidal alkaloid 3 β, 20 α-diamino-pregn-5-ene (kurchamine) obtained from the stem bark of Holarrhena antidysenterica is reported to have appreciable amoebicidal activity. Its three stereoisomers namely 3 α, 20 β-diamino-pregn-5-ene, 3 β, 20 β-diamino-pregn-5-ene and 3 α,20 α-diamino-pregn-5-ene and their intermediate stereoisomeric monoamino pregnene alkaloids namely 3 β-amino-pregn-5-ene-20-one, 3 α-amino-pregn-5-ene-20-one, 20 α -amino-pregn-5-ene-3 β-ol, 20 β-amino-pregn-5-ene-3 β-ol were synthesized. The natural stereoisomer and synthesized diamino and monoamino stereoisomers were N-methylated and all the compounds were evaluated for amoebicidal activity comparison. The natural stereoisomer 3 β,20 α-diamino-pregn-5-ene (kurchamine) was found to be superior than other stereoisomers and N-methylation was found to have insignificant effect on amoebicidal activity of stereoisomers. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
36. Defining the molecular properties of N-nitrosodimethylamine (NDMA) precursors using computational chemistry
- Author
-
Alexandra Simperler, Michael R. Templeton, Li Ling, Tom Bond, Wenhui Gan, Nigel Graham, and Xin Yang
- Subjects
Technology ,Environmental Engineering ,HALOGENATED DBPS ,CHLORINATION ,0208 environmental biotechnology ,DRINKING-WATER ,Environmental Sciences & Ecology ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,0905 Civil Engineering ,chemistry.chemical_compound ,Partial charge ,Engineering ,WASTE-WATER ,Computational chemistry ,N-Nitrosodimethylamine ,Molecular descriptor ,0399 Other Chemical Sciences ,Organic chemistry ,Moiety ,DISINFECTION BY-PRODUCTS ,Dimethylamine ,Chloramination ,0105 earth and related environmental sciences ,Water Science and Technology ,BASIS-SETS ,Science & Technology ,Chemistry ,NITROSAMINE PRECURSORS ,Engineering, Environmental ,CHLORAMINATION ,020801 environmental engineering ,Bond length ,Conessine ,0907 Environmental Engineering ,WATER-TREATMENT ,Physical Sciences ,Water Resources ,Life Sciences & Biomedicine ,TERTIARY-AMINES ,Environmental Sciences - Abstract
N-Nitrosodimethylamine (NDMA) is a potent carcinogen and can be produced during chloramination of drinking water and wastewater. Computational chemistry methods were used for the first time to calculate molecular descriptors for 64 NDMA precursors containing a dimethylamine (DMA) moiety. Descriptors were partial charge, bond length and pKa of the DMA nitrogen and planarity of the DMA group. Precursors classified on the basis of chemical functionality showed distinct relationships between partial charge and NDMA formation. Quaternary amines and tertiary amines with the DMA bonded to -COR and -CSR groups had a combination of low NDMA formation and high partial charge. The most potent NDMA precursors are tertiary amines with an acidic hydrogen and electron-donating group α and β to the DMA respectively. They also have comparable molecular descriptors: relatively negative partial charges, low planarity values, high bond lengths and pKa values from ∼8.3–10.1. A literature search identified 233 potential NDMA precursors that have never been tested experimentally. Of these chemicals 60% are therapeutics, 13% veterinary therapeutics and 10% natural products. Analysis combining qualitative assessment of chemical functionality and computational calculation of molecular descriptors successfully identified rivastigmine, a therapeutic, and conessine, a naturally occurring species, whose NDMA yields were determined experimentally to be 83.3 ± 0.5% and 42.3 ± 1.8% mol mol−1, respectively. This study defines the molecular properties associated with reactive NDMA precursors and the origin and identity of those amines which contribute to NDMA formation in drinking water.
- Published
- 2017
37. Activity of conessine at various temperatures and pH on inhibition of germination of Bacillus cereus and Bacillus stearothermophilus spores
- Author
-
Bogne Kamga Patrice, Etoa Franois-Xavier, Ronald Bayo James, Voundi Olugu Steve, and Nyegue Maximilienne
- Subjects
biology ,fungi ,Bacillus cereus ,Plant Science ,biology.organism_classification ,Microbiology ,Endospore ,Spore ,Agar plate ,Conessine ,chemistry.chemical_compound ,Infectious Diseases ,Cereus ,chemistry ,Germination ,bacteria ,Bacterial spore ,Food science - Abstract
This work reports the activity (at various conditions) of conessine isolated from methanolic extract of Holarrhena floribunda, on the inhibition of the germination of two Bacillus spores species. This activity was studied by treating spores of Bacillus cereus T and Bacillus stearothermophilus CNCH 5781 with effective concentrations of conessine at various temperature, pH and treatment times. The inhibition of germination was evaluated by the culture of treated spores on agar medium and the number of colony obtained was compared with that of control culture (not treated with conessine). We found that conessine used at 50 and 100 µg/ml for 20 min each decreased considerably the germination of spore of B. cereus T and B. stearothermophilus CNCH 5781. The maximum temperature of conessine activity for B. cereus T was at 30 and 60°C for B. stearothermophilus CNCH 5781 spores. Furthermore, the activity of conessine was sensitive to pH change and was more effective at pH 6 on both bacterial spore strains. The treatment of spores with conessine at various lengths of time demonstrated that, the activity of the compound on both bacterial spores was strongly related to the bacterial species. This study suggested that the activity of conessine on the inhibition of germination of Bacillus spore depends on physico-chemical factors and the bacterial species.
- Published
- 2014
38. In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice.
- Author
-
Kitanaka, Junichi, Kitanaka, Nobue, Hall, F. Scott, Amatsu, Yukie, Hashimoto, Kotaku, Hisatomi, Erina, Kitao, Eri, Mimura, Mari, Nakamura, Miyu, Ozawa, Rena, Sato, Miho, Tagami, Kenta, Uhl, George R., and Takemura, Motohiko
- Subjects
- *
ANTIHISTAMINES , *HISTAMINE receptors , *HISTAMINE , *MICE - Abstract
• Histamine H 3 receptor antagonists attenuated METH-induced hyperlocomotion in mice. • H 1 antagonists inhibited effect of H 3 antagonists on METH-induced behavior. • H 3 antagonists may be considered as candidates for treatment of METH actions. A single administration with METH (3 mg/kg) induced a hyperlocomotion in male ICR mice. Pretreatment of mice with pitolisant, a histamine H 3 receptor antagonist (5 and 10 mg/kg), for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle (saline)-pretreated subjects. Pretreatment of mice with the histamine H 3 receptor antagonists JNJ-10181457 (5 and 10 mg/kg) or conessine (20 mg/kg), also showed similar inhibitory effects on METH-induced hyperlocomotion, similar to pitolisant. No significant change in locomotion was observed in mice pretreated with pitolisant, JNJ-10181457, or conessine alone. The pitolisant (10 mg/kg) action on METH-induced hyperlocomotion was completely abolished by the histamine H 1 receptor antagonist pyrilamine (10 mg/kg), but not by the peripherally acting histamine H 1 receptor antagonist fexofenadine (20 mg/kg), the brain-penetrating histamine H 2 receptor antagonist zolantidine (10 mg/kg), or the brain-penetrating histamine H 4 receptor antagonist JNJ-7777120 (40 mg/kg). Pretreatment with a histamine H 3 receptor agonist immepip (10 mg/kg) augmented METH--induced behavior, including hyperlocomotion and stereotyped biting, and combined pretreatment with pitolisant (10 mg/kg) significantly attenuated stereotyped biting. These observations suggest that pretreatment with histamine H 3 receptor antagonists attenuate METH-induced hyperlocomotion via releasing histamine after blocking H 3 receptors, which then bind to the post-synaptic histamine receptor H 1 (but not H 2 or H 4). It is likely that activation of brain histamine systems may be a good strategy for the development of agents, which treat METH abuse and dependence. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
39. Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors
- Author
-
Yin Shi, Guofei Jin, Weiwei Xue, Zhong-Duo Yang, Xiaojun Yao, and Jie Sheng
- Subjects
biology ,Molecular model ,Stereochemistry ,Chemistry ,Active site ,Biological activity ,General Chemistry ,Acetylcholinesterase ,Conessine ,chemistry.chemical_compound ,biology.protein ,Nucleophilic substitution ,medicine ,IC50 ,Huperzine A ,medicine.drug - Abstract
New isoconessimine derivatives were synthesized from conessine (1) and evaluated as acetylcholinesterase (AChE) inhibitors. The derivatives were prepared via two reaction steps, N-demethylation and nucleophilic substitution. All of the synthesized derivatives exhibited more potential anti-acetylcholinesterase activities than conessine (1) (IC50=16 mu molL(-1)) and isoconessimine (2) (IC50>300 mu molL(-1)). Compound 7b (3-[methyl-[2-(4-nitrophenoxy)ethyl]amino]con-5-enine) showed the most potent inhibitory activity with an IC50 of 110 nmol/L which is close to that of reference compound huperzine A (IC50=70 nmol/L). The mode of AChE inhibition by 7b was reversible and non-competitive. In addition, molecular modeling was performed to explore the binding mode of inhibitor 7b at the active site of AChE and the results showed that 7b could be docked into the acetylcholinesterase active site and compound 7b had hydrophobic interactions with Trp279 and Leu282.
- Published
- 2013
40. Evaluation of phytochemical and pharmacological aspects of Holarrhena antidysenterica (Wall.): A comprehensive review
- Author
-
Amit Vashishtha, Brijesh Rathi, Aishwarye Sharma, N.V.S.R.K. Prasad, P. Hemalatha Reddy, and Snehadri Sinha
- Subjects
Phytochemistry ,biology ,Apocynaceae ,Traditional medicine ,fungi ,food and beverages ,Pharmacognosy ,biology.organism_classification ,Conessine ,chemistry.chemical_compound ,Phytochemical ,chemistry ,Botany ,Natural Product Research ,Medicinal plants ,Holarrhena - Abstract
Medicinal plants are generating an ever-increasing amount of interest due to the effectiveness, low cost and minimal side-effects associated with drugs derived from them. Holarrhena antidysenterica (syn. H. pubescens) WALL., belonging to the family Apocynaceae, is commended for the medicinal applications of its stem bark, leaves and seeds in Ayurveda. During the past century, studies on the phytochemical and pharmacological nature of the plant have yielded important results regarding the chemical constituents present and have also verified the traditionally claimed properties associated with the plant viz. analgesic, antibacterial, anti-diarrhoeal, anti-amoebic, anti-inflammatory and anti-haemorrhoidal activities. Moreover, recently some other properties have also been discovered viz. anti-malarial, anti-diabetic, anti-oxidant, anti-urolithic, anti-mutagenic, CNS-stimulating, Angiotensin-converting-enzyme inhibitory and acetylcholinesterase inhibitory activity. This review discusses the findings of studies on the aforementioned properties of the plant in detail and 68 alkaloids isolated from various parts of plant to justify its widespread use in the treatment of a variety of diseases and suggests future lines of research.
- Published
- 2013
41. Pharmacokinetics and pharmacodynamics of a novel Acetylcholinesterase Inhibitor, DMNG-3
- Author
-
Zhong-Duo Yang, Peng Tang, Guo-Di Ma, Xin-Guo Zhang, and Fei Kou
- Subjects
Male ,medicine.drug_class ,Scopolamine ,Pharmacology ,01 natural sciences ,High-performance liquid chromatography ,Antioxidants ,Cholinergic Antagonists ,chemistry.chemical_compound ,Mice ,Random Allocation ,Alkaloids ,Pharmacokinetics ,Oral administration ,Memory ,medicine ,Avoidance Learning ,Distribution (pharmacology) ,Animals ,Large intestine ,Tissue Distribution ,Mice, Inbred ICR ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Chemistry ,General Neuroscience ,010401 analytical chemistry ,General Medicine ,Small intestine ,0104 chemical sciences ,Conessine ,medicine.anatomical_structure ,Acetylcholinesterase inhibitor ,DMNG-3 ,step-down passive avoidance test ,Area Under Curve ,Flavanones ,Cholinesterase Inhibitors ,HPLC ,pharmacokinetics ,Half-Life - Abstract
DMNG-3 (3β-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step‑down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography (HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol‑water (70:30, v/v) at a flow rate of 1.0 ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45%. Our results showed oral administration of DMNG-3 (10, 25, 50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half-life (T1/2) was 14.07±1.29, 15.87±1.03 h, and the total clearance (CL) values were 0.70±0.11, 0.78±0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future.
- Published
- 2016
42. Chromatographic analysis of bioactive markers inVidangarista, an ayurvedic polyherbal formulation
- Author
-
Parameswaran Sandhya and Pallavi S. Bhujbal
- Subjects
Conessine ,chemistry.chemical_compound ,Chromatography ,Linear relationship ,chemistry ,Clinical Biochemistry ,Gallic acid ,Routine analysis ,Biochemistry ,Analytical Chemistry - Abstract
Vidangarista is an ayurvedic polyherbal formulation officially recorded in the Ayurvedic formulary of India and used as an anthelmintic. The herbal formulation contains many plant constituents, and hence a large number of markers should be quantified to assess its quality. This paper reports the standardization of Vidangarista by HPTLC analysis for the presence of the biomarkers gallic acid and conessine. Each marker compound showed a linear relationship with an average r2 = 0.99 in the concentration range studied. The proposed method was found to be precise, specific, and accurate, with a recovery of 99–101%, and hence can be used for routine analysis of this formulation.
- Published
- 2012
43. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice
- Author
-
Mariane Ferreira-Santos, Gessynger Morais-Silva, Marcelo Tadeu Marin, Universidade Estadual Paulista (Unesp), and Universidade Federal de Uberlândia (UFU)
- Subjects
0301 basic medicine ,Monoamines ,Male ,Alcohol addiction ,Nigrostriatal pathway ,Pharmacology ,Neurotransmission ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Alkaloids ,Dopamine ,medicine ,Animals ,Chromatography, High Pressure Liquid ,Analysis of Variance ,Neurotransmitter Agents ,Dose-Response Relationship, Drug ,Ethanol ,Conessine ,Dopaminergic ,Brain ,Central Nervous System Depressants ,Homovanillic Acid ,Conditioned place preference ,Ventral tegmental area ,Psychostimulation ,030104 developmental biology ,medicine.anatomical_structure ,H3 receptor antagonist ,chemistry ,Dopaminergic pathways ,3,4-Dihydroxyphenylacetic Acid ,Conditioning, Operant ,Neuroscience ,030217 neurology & neurosurgery ,Locomotion ,medicine.drug ,Histamine H3 Antagonists - Abstract
Made available in DSpace on 2018-12-11T16:41:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-15 Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway. Laboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista-UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP Institute of Biomedical Sciences Federal University of Uberlândia (UFU) Laboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista-UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP
- Published
- 2015
44. Inhibition of polyamine biosynthesis for toxicity control in Serratia marcescens strain WW4 by targeting ornithine decarboxylase: a structure-based virtual screening study
- Author
-
Pramod Kumar Yadav, Kalyani Dhusia, Pramod W. Ramteke, and Rohit Farmer
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Ornithine ,Computer Science Applications ,Ornithine decarboxylase ,Spermidine ,03 medical and health sciences ,chemistry.chemical_compound ,Conessine ,030104 developmental biology ,Enzyme ,chemistry ,Biosynthesis ,Biochemistry ,Docking (molecular) ,Drug Discovery ,Polyamine - Abstract
Ornithine decarboxylase (ODC) enzyme, catalyses the decarboxylation of ornithine to form spermidine which is a committed step in the biosynthesis of polyamines. Here, in the present work, structure of ODC was modelled and studied for its active site. The stability of modelled structure was revalidated by the molecular dynamics simulation at 50 nano second time scale. 142 Natural products of Indofine Herbal Ingredient library from ZINC database were screened using Autodock Vina for the identification of potential leading herbal inhibitors. The results obtained from docking showed that Conessine is best inhibiting candidate with docking affinity of –9.7 Kcal/mol. Conessine is an alkaloid which proves its immense importance as metabolites. Thus, polyamine being harmful when synthesised in excess are necessary to be controlled at their genesis. Therefore, conessine might be a potential inhibitor for toxicity control in plant growth promoting rhizobacteria.
- Published
- 2018
45. Novel H3 receptor antagonists with improved pharmacokinetic profiles
- Author
-
Andrew J. Grottick, Michelle D. Pulley, Rena Hayashi, Jonathan A. Covel, Brian J. Hofilena, Guilherme Pereira, William Thomsen, Vincent J. Santora, Marissa Suarez, Jeff Edwards, Albert S. Ren, Jodie Lorea, Michael I. Weinhouse, Graeme Semple, Erin K. Hauser, John Frazer, and Jason B. Ibarra
- Subjects
Central Nervous System ,Stereochemistry ,Chemistry, Pharmaceutical ,Clinical Biochemistry ,Histamine Antagonists ,Pharmaceutical Science ,Pharmacology ,Binding, Competitive ,Biochemistry ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Alkaloids ,Pharmacokinetics ,In vivo ,Drug Discovery ,Animals ,Receptors, Histamine H3 ,Potency ,Receptor ,Molecular Biology ,Natural product ,Molecular Structure ,Organic Chemistry ,Rats ,Kinetics ,Conessine ,Models, Chemical ,chemistry ,Drug Design ,Molecular Medicine ,Histamine H3 receptor - Abstract
A new series of H 3 antagonists derived from the natural product Conessine are presented. Several compounds from these new series retain the potency and selectivity of earlier diamine based analogs while exhibiting improved PK characteristics. One compound ( 3u ) demonstrated functional antagonism of the H 3 receptor in an in vivo pharmacological model.
- Published
- 2008
46. Construction of quaternary centres for natural polycycles: The Pauson–Khand approach
- Author
-
Eduardo Arnaiz, Gema Domínguez, Delbrin Abdi, Javier Pérez Castells, and Jaime Blanco-Urgoiti
- Subjects
Reaction conditions ,Organic Chemistry ,chemistry.chemical_element ,Molecular sieve ,Ring (chemistry) ,Biochemistry ,Rhodium ,Inorganic Chemistry ,Conessine ,chemistry.chemical_compound ,chemistry ,Cobalt carbonyl ,Materials Chemistry ,Organic chemistry ,Physical and Theoretical Chemistry ,Cobalt ,Quaternary carbon - Abstract
Construction of quaternary carbons is a challenge in PK chemistry, with few precedents in the literature. Starting from suitable functionalized enynes including an aromatic ring that templates the reaction, polycyclic ketones are obtained with a quaternary carbon. Special reaction conditions are necessary including the use of molecular sieves and co-catalysis with rhodium complexes jointly with cobalt carbonyl. The products obtained are intermediates in the synthesis of various natural products like the Hamigeran family and the steroidic alkaloid Conessine.
- Published
- 2008
47. Development and Validation of a Visible Absorption Densitometry Method for Quantitation of Conessine in Holarrhena antidysenterica (Kurchi)
- Author
-
Arun M Prajapati and Rakesh Patel
- Subjects
Pharmacology ,Absorption (pharmacology) ,Chromatography ,biology ,Chemistry ,Silica gel ,Repeatability ,biology.organism_classification ,Analytical Chemistry ,Conessine ,chemistry.chemical_compound ,Brown color ,Environmental Chemistry ,Densitometry ,Agronomy and Crop Science ,Quantitative analysis (chemistry) ,Food Science ,Holarrhena - Abstract
A selective, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been proposed for the analysis of conessine in Holarrhena antidysenterica. The method involves visible densitometric evaluation of conessine resolving it by HPTLC on aluminium-based silica gel plates. For visible densitometric evaluation, peak areas were recorded at 520 nm after the resolved bands were derivatized with Dragendorff's reagent and then sprayed with a 10 solution of aqueous sodium nitrite which resulted in reddish brown color. The correlation between the concentration and area was found to be linear within the range of 10 to 60 ng/spot. The method was validated for precision (interday and intraday), repeatability, and accuracy. Mean recovery for conessine was 98.34100.25. The method was applied for the quantitation of conessine in Kurchi. The proposed HPTLC method was found to be precise, specific, sensitive, and accurate and can be used for routine analysis of Kurchi.
- Published
- 2008
48. Targeting Antibiotic Resistant Salmonella enterica: Bio-matrix Based Selection and Bioactivity Prediction of Potential Nutraceuticals
- Author
-
Rajesh Arora, Ankit Tanwar, Pallavi Thakur, Raman Chawla, Sarita Jaiswal, Ankita Singh Chakotiya, Rakesh Sharma, Haider A. Khan, and Rajeev Goel
- Subjects
biology ,Traditional medicine ,Andrographolide ,General Medicine ,biology.organism_classification ,Symptomatic relief ,Microbiology ,Conessine ,chemistry.chemical_compound ,chemistry ,Salmonella enterica ,Abrus precatorius ,Terminalia arjuna ,Andrographis paniculata ,Holarrhena - Abstract
Aim: Potential herbal leads as novel therapeutic alternatives against Multi-Drug Resistant Salmonella enterica serovar typhimurium were investigated and validated by mol inspiration. Methodology: The present study utilizes an in silico ‘Herbal Informatics’ model which deploys dynamic search protocols, priority indexing and systemic categorization for rationale based selection of nutraceuticals targeting the critical virulence factors of Multi-Drug Resistant Salmonella enterica serovar typhimurium. Furthermore, in silico biochemical activity prediction was conducted using ‘Mol inspiration’ chemiinformatics tool, so as to propose the drug likeliness of selected natural plant products. Results: Out of the 05 selected bioactivity parameters of Salmonella enterica, lipo-polysaccharide inhibition exhibited maximum relevance as physiological target i.e., 65%, followed by other parameters like enterochelin inhibition, Type III secretory system inhibition, Superoxide dismutase inhibition and Symptomatic relief provision. The binary matrix analysis of database of 50 plants identified using classical bioprospection filtered 28 herbals which exhibited probable potential to mitigate 03 or more virulence factors. The weightage matrix analysis further scrutinized the selection upto 10 herbals having a score more than median weightage matrix score i.e., 14.98. The optimization of data on a scale of 0-1 using fuzzy score matrix analysis led to the final selection of 10 herbals i.e., Abrus precatorius, Azadirachta indica, Camellia sinensis, Holarrhena antidysenterica, Andrographis paniculata, Adhatoda vasica, Euphorbia hirta, Ocimum sanctum, Terminalia arjuna and Terminalia belerica. In silico Bioactivity prediction analysis of predominant phytoconstituents of selected herbals revealed Holarrhena antidysenterica (Conessine), Andrographis paniculata (Andrographolide), Euphorbia hirta (Amyrin) and Terminalia arjuna (Arjunolic acid) exhibiting drug likeliness with their targeted action as a GPCR Ligand, Nuclear Receptor Ligand or Protease inhibitor.
- Published
- 2015
49. Isolation, characterization and antiplasmodial activity of steroidal alkaloids from Funtumia elastica (Preuss) Stapf
- Author
-
Guédé Noël Zirihi, Bernard Bodo, Philippe Grellier, Frederick Guede-Guina, Lengo Mambu, Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de chimie et biochimie des substances naturelles, and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Plasmodium falciparum ,Clinical Biochemistry ,Pharmaceutical Science ,Fractionation ,Pharmacognosy ,MESH: Spectrometry, Mass, Electrospray Ionization ,Biochemistry ,Antimalarials ,chemistry.chemical_compound ,Alkaloids ,MESH: Apocynaceae ,MESH: Alkaloids ,Drug Discovery ,Animals ,MESH: Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Cytotoxicity ,Molecular Biology ,MESH: Plasmodium falciparum ,Stem bark ,Traditional medicine ,biology ,Apocynaceae ,MESH: Magnetic Resonance Spectroscopy ,Chemistry ,Alkaloid ,Organic Chemistry ,Biological activity ,General Medicine ,biology.organism_classification ,MESH: Antimalarials ,Conessine ,Funtumia elastica ,visual_art ,visual_art.visual_art_medium ,Molecular Medicine ,Bark - Abstract
International audience; Bioassay-guided fractionation of the EtOH extract of the stem bark of Funtumia elastica resulted in the isolation of four steroidal alkaloids, holarrhetine (1), conessine (2), holarrhesine (3) and isoconessimine (4). Their structures were determined on the basis of 1D- and 2D-NMR techniques and mass spectrometry. Compounds 1-4 exhibited in vitro antiplasmodial activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum with IC50 values ranging from 0.97 to 3.39 microM. They showed weak cytotoxicity against a rat cell line L-6 with IC50 values ranging from 5.13 to 36.55 microM.
- Published
- 2005
50. Comparison of anti amoebic activity of stereoisomeric diamino and monoamino pregnene alkaloids and their N-methylated analogs
- Author
-
K. K. Bhutani and R. M. Vaid
- Subjects
Conessine ,chemistry.chemical_compound ,Stem bark ,Pregnene ,chemistry ,biology ,Stereochemistry ,Steroidal alkaloid ,General Chemistry ,biology.organism_classification ,Holarrhena - Abstract
The steroidal alkaloid 3β, 20α-diamino-pregn-5-ene (kurchamine) obtained from the stem bark of Holarrhena antidysenterica is reported to have appreciable amoebicidal activity. Its three stereoisomers namely 3α, 20β-diamino-pregn-5-ene, 3β, 20β-diamino-pregn-5-ene and 3α,20α-diamino-pregn-5-ene and their intermediate stereoisomeric monoamino pregnene alkaloids namely 3β-amino-pregn-5-ene-20-one, 3α-amino-pregn-5-ene-20-one, 20α -amino-pregn-5-ene-3β-ol, 20β-amino-pregn-5-ene-3β-ol were synthesized. The natural stereoisomer and synthesized diamino and monoamino stereoisomers were N-methylated and all the compounds were evaluated for amoebicidal activity comparison. The natural stereoisomer 3β,20α-diamino-pregn-5-ene (kurchamine) was found to be superior than other stereoisomers and N-methylation was found to have insignificant effect on amoebicidal activity of stereoisomers.
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.