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Two new isopimarane diterpenes, 1α-hydroxy-14α-methoxyisopimara-8(9),15-diene (7) and 1α,14α-dihydroxyisopimara-8(9),15-diene (9) and eight known isopimarane diterpenes including (-)-sandaracopimaradiene (1), 6β-acetoxysandaracopimaradiene-9α-ol (2), sandaracopimaradiene-7β,9α-diol (3), sandaracopimaradiene-1α,9α-diol (4), 6β-acetoxysandaracopimaradiene-9α-ol-1-one (5), 6β-acetoxysandaracopimaradiene-1α,9α-diol (6), 6β,14α-dihydroxyisopimara-8(9),15-diene (8), and 6β,14β-dihydroxyisopimara-8(9),15-diene (10) were isolated from hexane fraction of Kaempferia galanga ethanol extract. Compounds 5, 6, 8, and 9 exerted the good anti-inflammatory effect on lipopolysaccharide-stimulated nitric oxide production from RAW264.7 cells with IC 50 of 11.2, 7.7, 14.3, and 12.1 μM, respectively. These four compounds inhibited nitric oxide synthase (iNOS) mRNA expression. Compounds 5 and 6 also suppressed cyclooxygenase 2 (COX-2) mRNA expression; in addition, compound 6 had mild inhibitory effect on TNF-α mRNA. Among these compounds, 5 dramatically inhibited iNOS and COX-2 mRNA expression. The influential structures were proposed to be oxygen substitute at C-1, C-6, and α-OH at C-14., (© 2019 John Wiley & Sons, Ltd.)

Background: Galatella is a genus in the family Asteraceae, represented by 35-45 species. Considering the high effectiveness of the ethyl acetate (EtOAc) fraction of G. grimmii against Mycobacterium tuberculosis (MIC = 0.5 µg/mL), a bioassay-directed fractionation of this extract was carried out. Methods: The methanolic extract of the aerial parts of G. grimmii was obtained using maceration, then it was suspended in water and partitioned with petroleum ether, dichloromethane (CH2Cl2), EtOAc, and n-butanol (n-BuOH), successively. The most potent fraction (EtOAc), was selected for further isolation by Sephadex LH–20 and semi-preparative HPLC to obtain active compounds. Results: Fractionation of the EtOAc solvent fraction resulted in the characterization of five compounds, among them, compounds 1 and 2 showed the highest anti-mycobacterial effects with MICs of 0.062 and 1.00 µg/mL against H37Rv M. tuberculosis, respectively, which were higher than those of rifampin (MIC of 1.25 µg/mL) and isoniazid (MIC of 0.31 µg/mL), as positive controls. Also, compound 1 ​​inhibited all tested strains of drug-resistant Mycobacterium (MDR and XDR). Notably, the isolated compounds have been reported for the first time from G. grimmii. Conclusion: Due to the potent anti-mycobacterial effect of isolated compounds from G. grimmii, this study could pave the way for developing a novel class of natural anti-tuberculosis compounds. [ABSTRACT FROM AUTHOR]

Background: The successful launch of icaritin, a therapeutic drug for liver cancer derived from Epimedium brevicornu, has provided new impetus for the development of prenylated flavonoids in the field of oncology. Flemingia macrophylla is reported to contain characteristic prenylated flavonoids which can regulate the p53 protein. We aimed to isolate these constituents and conduct activity evaluation, structure–activity relationship, and mechanism studies to provide candidate compounds for antitumor drug development. Methods: In this study, chromatographic techniques combined with spectroscopic methods were used to separate, purify, and identify the constituents of Flemingia macrophylla methanol extract. The cytotoxic activity of the constituents was evaluated using an MTT assay with A549 and H1975 cells as the model. The binding mechanism between the compounds and the p53 protein was investigated with molecular docking and validated with cellular thermal shift assay (CETSA). Western blotting (WB) was employed to detect the expression of p53 protein and apoptosis-related proteins in cells. Results: Chiral HPLC separation of racemates 1 and 7 provided two pairs of undescribed enantiomers (1a/1b and 7a/7b), along with eight known compounds (2 − 9) isolated from Flemingia macrophylla roots. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of the enantiomers were determined from experimental and calculated electronic circular dichroism data. Compounds 1 − 7, and the non-prenyl analogues 10 − 13, were evaluated for cytotoxic activity against the human lung cancer A549 and H1975 cell line. Compounds 5 − 7 displayed better cytotoxicity than the positive control icaritin in A549 and H1975, with IC50 values ranging from 4.50 to 19.83 μmol·L-1 and < 5 μmol·L-1, respectively. The structure–activity relationships of the chromone or flavonoid analogues against A549 cells were discussed. Molecular docking results demonstrated that compound 7a has strong interaction with p53 and WB indicated that 7a induced apoptosis by increasing the p53 protein, decreasing the anti-apoptotic protein Bcl-2, and activating the caspase family in A549 cells. These results suggest that prenylated flavonoids are potential p53 protein activators. Conclusion: This study demonstrates that Flemingia macrophylla is rich in prenylated flavonoid constituents, among which compounds 5 and 7 exhibited significant cytotoxic activity against A549 cells and served as reference candidates for the design and development of prenylated compounds as antitumor therapeutic drugs. Highlights: Two pairs of undescribed enantiomers (1a/1b and 7a/7b) were isolated from Flemingia macrophylla. Prenylated flavonoids 5 − 7 exhibited significant cytotoxicity against A549 cells. Structure-activity relationship study revealed that the presence of B-ring and 2ʹ-OH substitution and the cyclization of 6/8-pentenyl group with 7-OH were beneficial for cytotoxicity. Molecular docking results showed that Cys124 and Cys277 were the key amino acid residues for binding. Compound 7a induced apoptosis of A549 cells by activating the p53 protein. [ABSTRACT FROM AUTHOR]

Indonesia is among the countries with the most significant biodiversity globally. Jamu, the traditional medicine of Indonesia, predominantly uses herbal materials and is an integral component of the Indonesian healthcare system. The present study reviewed the ethnobotanical data of seven Indonesian Euphorbiaceae species, namely Euphorbia atoto, E. hypericifolia, Homalanthus giganteus, Macaranga tanarius, Mallotus mollissimus, M. rufidulus, and Shirakiopsis indica, based on the RISTOJA database and other literature sources. An antimicrobial screening of the plant extracts was performed in 15 microorganisms using the disk diffusion and broth microdilution methods, and the antiproliferative effects were examined in drug-sensitive Colo 205 and resistant Colo 320 cells by the MTT assay. The antimicrobial testing showed a high potency of M. tanarius, H. giganteus, M. rufidulus, S. indica, and E. atoto extracts (MIC = 12.5–500 µg/mL) against different bacteria. In the antitumour screening, remarkable activities (IC50 0.23–2.60 µg/mL) were demonstrated for the extracts of H. giganteus, M. rufidulus, S. indica, and E. atoto against Colo 205 cells. The n-hexane extract of E. atoto, with an IC50 value of 0.24 ± 0.06 µg/mL (Colo 205), was subjected to multistep chromatographic separation, and 24-methylene-cycloartan-3β-ol, jolkinolide E, tetra-tert-butyl-diphenyl ether, α-tocopherol, and β-sitosterol were isolated. [ABSTRACT FROM AUTHOR]

As part of our search for new secondary metabolites from Macaranga hurifolia Beille, a phytochemical investigation was carried out on the fruits that led to the isolation and characterization of two new prenylated flavonol derivatives named macafolias A (1) and B (2), along with five known compounds. Their chemical structures were established on the basis of extensive analysis of their 1–D and 2–D NMR (1H, 13C, APT, COSY, HSQC and HMBC) in conjunction with mass spectroscopy and by comparison with data from the literature. The in vitro assay of the antibacterial potency of the crude extract, fractions and some pure compounds were evaluated against a wide range of bacteria strains. [ABSTRACT FROM AUTHOR]

Schistosomiasis control remains a public health concern, and there is a need to evaluate new strategies for targeting larval and adult stages of the parasite. As Pedilanthus tithymaloides is empirically used to treat schistosomiasis, it becomes essential to know its effective action scientifically. This study assessed the cercaricidal and schistosomicidal activity of P. tithymaloides stem barks raffia wine extract (RwPt) and hydroethanolic extract (HePt). Different concentrations of these extracts were tested against cercariae (31.25–1000 μg/mL) and adult worms (62.5–2000 μg/mL) of Schistosoma mansoni. Niclosamide-olamine 5% (1 μg/mL) and praziquantel (10 μg/mL) were used as pharmacological controls. Cercariae viability was determined every 30 min for 180 min, and adult worms' motor activity and viability after 24 and 48 h incubation. In addition, cytotoxicity and phytochemical analysis were performed. HePt was lethal to cercariae and adult worms with LC50 of 73.91 μg/mL after 60 min of incubation and 731.17 μg/mL after 48 h of incubation, respectively. Furthermore, a significant reduction of 94.44% in motor activity was observed in surviving worms at the concentration of 2000 μg/mL. RwPt was less effective on S. mansoni cercariae with an LC50 of 617.86 μg/mL after 180 min and on adult worms with a mortality rate of 9.83% at 2000 μg/mL for 48 h incubation. Both extracts showed a weak cytotoxicity profile with an IC50 of 983.50 μg/mL for HePt and more than 1000 μg/mL for RwPt. The LC-MS analysis of HePt allowed the detection of two annotated diterpenoids. Based on the selectivity index, the hydroethanolic extract of P. tithymaloides stem barks disclosed an intense cercaricidal activity and a moderate schistosomicidal effect with low cytotoxicity. These findings may support the potential use of Pedilanthus tithymaloides as a natural product or a source of natural-derived compounds for interrupting schistosomiasis transmission. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the petroleum ether and methylene chloride extracts of the stems of Euphorbia tithymaloides L. (Euphorbiaceae) afforded the triterpenes friedelane-3β-ol, 3-oxo-friedelane, euphane-7, 24-diene, 3β-ol (butyrospermol), and euphane -7, 25-diene, 3, 24-β-diols in addition to the diterpene derivative 1 a, 13 β, 14 a-trihydroxy-3 β, 7 β-dibenzenzoyloxy-9 β, 15 β-diacetoxyjatropha-5, 11-E-diene and the phytosterol β-sitosterol. The structures of the isolated compounds were established depend on spectroscopic and chemical evidences. The petroleum ether, methylene chloride, and methanolic extracts of the stems of E. tithymaliodes L. were tested in vitro by determining their action on oxidative stress status of rat liver homogenate for their hepatoprotective activity in addition, the pet ether extract was tested in vivo for its hepatoprotective activity and diterpene derivative was tested in vitro for cytotoxic activity. [ABSTRACT FROM AUTHOR]

Medicinal plants are the chief components in the different oriental formulations in different traditional medical systems worldwide. As a thriving source of medicine, the medicinal plants with antituberculosis (TB) properties inspire the pharmacists to develop new drugs based on their active components or semimetabolites. In the present review, the anti-TB medicinal plants were screened from the scientific literatures, based on the botanical classification and the anti-TB activity. The obtained anti-TB medicinal plants were categorized into three different categories, viz., 159 plants critically examined with a total 335 isolated compounds, 131 plants with their crude extracts showing anti-TB activity, and 27 plants in literature with the prescribed formula by the traditional healers. Our systemic analysis on the medicinal plants can assist the discovery of novel and more efficacious anti-TB drugs. [ABSTRACT FROM AUTHOR]

Introduction: Macaranga species are traditionally used for the treatment and management of coughing, fungal infection, and wounds. In this study, the phytochemical screening and antibacterial activities of nine crude extracts from Macaranga conglomerata, Macaranga kilimandscharica and Macaranga capensis were determined against 13 bacterial strains expressing multi-drug resistance (MDR) phenotypes. Methods: Phytochemical screening of the extracts were carried out according to the standard methods, while the iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the plants extracts. Results: Flavonoids, terpenoids, saponins and coumarins were the major secondary metabolites found in all the plant extracts. The results of antibacterial studies revealed that all the plant extracts displayed good activities with MIC values ranging from 4 - 128 μg/mL against the tested micro-organisms. Most of the extracts exhibited a bactericidal effect against E. coli, E. aerogenes, K. pneumoniae, P. stuartii, P. aeruginosa, and S. aureus with MBC/MIC ratio ≤ 4. In the presence of efflux pump inhibitor (PaβN), the inhibition potency of all the crude extracts against the tested bacterial strains were substantially enhanced. It is worth noting that the activities of MKL, MCL, and MCR towards P. stuartii (NEA16), E. aerogenes (ATCC13048), and K. pneumoniae (KP55), respectively were improved by more than 8-fold in the presence of PAβN. Conclusion: The findings of this study indicated the possibility of using all the tested plant extracts as a source of therapeutic agents in the fight against multi-drug resistant bacteria. [ABSTRACT FROM AUTHOR]

Background. Infections by microbes (viruses, bacteria, and fungi) and parasites can cause serious diseases in both humans and animals. Heavy use of antimicrobials has created selective pressure and caused resistance to currently available antibiotics, hence the need for finding new and better antibiotics. Natural products, especially from plants, are known for their medicinal properties, including antimicrobial and anthelmintic activities. Geoclimatic variation, together with diversity in ethnomedicinal traditions, has made the Himalayas of Nepal an invaluable repository of traditional medicinal plants. We studied antiviral, antibacterial, antifungal, and anthelmintic activities of medicinal plants, selected based upon ethnobotanical evidence. Methods. Ethanolic and methanolic extracts were tested (1) on a panel of microbes: two Gram-positive bacteria (Staphylococcus aureus and Listeria innocua), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Shigella sonnei), and one fungal species: Candida albicans; (2) against three different viruses: yellow fever, chikungunya, and enterovirus; and (3) on the nematode Caenorhabditis elegans. Also, cytotoxicity was assessed on human hepatoma (Huh), rhabdosarcoma (RD), and Vero (VC) cell lines. Results. Of 18 plants studied, Ampelocissus tomentosa and Aleuritopteris anceps inhibited S. aureus (MIC 35 μg/mL and 649 μg/mL, respectively) and Pseudomonas aeruginosa (MIC 15 μg/mL and 38 μg/mL, respectively). Rhododendron arboreum and Adhatoda vasica inhibited S. enterica (MIC 285 μg/mL and 326 μg/mL, respectively). Kalanchoe pinnata, Ampelocissus tomentosa, and Paris polyphylla were active against chikungunya virus, and Clerodendrum serratum was active against yellow fever virus (EC50 15.9 μg/mL); Terminalia chebula was active against enterovirus (EC50 10.6 μg/mL). Ampelocissus tomentosa, Boenninghausenia albiflora, Dichrocephala integrifolia, and Kalanchoe pinnata significantly reduced C. elegans motility, comparable to levamisole. Conclusions. In countries like Nepal, with a high burden of infectious and parasitic diseases, and a current health system unable to combat the burden of diseases, evaluation of local plants as a treatment or potential source of drugs can help expand treatment options. Screening plants against a broad range of pathogens (bacteria, viruses, fungi, and parasites) will support bioprospecting in Nepal, which may eventually lead to new drug development. [ABSTRACT FROM AUTHOR]

Purpose: Daphne mucronata Royle grown in Iran has shown anticancer activities against different cancer cell lines. Therefore, within this study, we investigate the phytochemical pattern of this plant. Method: Phytochemical investigation was done using standard column chromatography system: The structures were recognized by the interpretation of one and two-dimensional nuclear magnetic resonance (NMR) spectra and the help of High-Resolution Electrospray Ionization Mass spectroscopy (HR-ESIMS) and Infrared spectroscopy (IR) data. Stereochemistry was determined using 2D and 3D NOESY, and comparison of coupling constant values with literature. The absolute configuration was determined and confirmed using specific rotation and electronic circular dichroism experiments. Cytotoxicity was done against HeLa cells by standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Luciferase assay was used to check if the compounds can inhibit the activation of cancer-related signaling pathways. Molecular docking simulation was done for biological activity evaluation and to examine the interaction of the ligand with each of the proteins. Results: A new sesquiterpenoid, 4,11(12)-guiadiene-1-ol-3-one (4), together with eight specialized metabolites, betulinic acid (1), coniferyl aldehyde (2), oleanolic acid (3), daphnetoxin (5), apigenin (7), syringin (8), and genkwanol A (9) were isolated and reported for the first time from the shoots of the plant. Compound 4 as an undescribed compound was submitted for cytotoxicity assay and showed moderate activity with the IC50 value of 51.3 ± 4.2 μM against HeLa cancer cells. It showed selective inhibition of Interleukin-6 mediated signal transducer and activator of transcription 3 pathway (STAT-3/ IL-6), and Smad protein / transforming growth factor beta (TGF-β) transcription factors when screened through an array of cancer signaling pathways. Molecular docking confirmed biological tests and showed the interaction with STAT3 and Smad proteins. Conclusion: An undescribed sesquiterpenoid: 4,11(12)-guiadiene-1-ol-3-one in addition to eight known compounds were isolated. The new sesquiterpene was evaluated for the luciferase assay on 14 main cancer-related signaling pathways and showed selective inhibition of STAT3/IL6, and Smad/ TGF-β transcription factors. Molecular docking simulation showed more interactions with STAT3 than Smad, which confirms better interaction of compound 4 with STAT3 than Smad proteins. [ABSTRACT FROM AUTHOR]

Metabolic disorders like diabetes mellitus, hypertension, dyslipidemia, and obesity are major medical problems globally. The incidence of these disorders has increased tremendously in recent years. Studies have demonstrated that plants with antioxidant and anti-inflammatory properties have beneficial effects on these disorders. One of these plants is Citrus hystrix DC, commonly known as kaffir lime. This review aims to present updates on the progress of research regarding the use of C. hystrix in metabolic disorders. Phytochemical compounds, including β-pinene, sabinene, citronellal, and citronellol, have been detected in the plant; and its extract exhibited potential antidiabetic, antihyperlipidemic and anti-obesity activity, as well as prevention of development of hypertension. These beneficial properties may be attributable to the presence of bioactive compounds which have therapeutic potential in treating these metabolic disorders. The compounds have the potential to be developed as candidate drugs. This review will assist in validating the regulatory role of the extract and its bioactive compounds on metabolic disorders, thus expediting future research in the area. [ABSTRACT FROM AUTHOR]

Background: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts. Methods: Compounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated. Results: Bioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G0/G1 and G2/M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6). Conclusion: The ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds. [ABSTRACT FROM AUTHOR]