An ethnopharmacological approach to evaluate antiparasitic and health-promoting abilities of Pueraria tuberosa (Willd.) DC. in livestock.

In eastern India, the tubers of Pueraria tuberosa (Willd.) DC. are used by the ethnic communities for its wide range of medicinal and nutritional value, especially to rejuvenate livestock health and to treat helminthiasis. The study is aimed to evaluate the ethnoveterinary medicinal importance of P. tuberosa as anthelmintic, to verify its nontoxic nature and identify the most potent phytoconstituents aided by in silico molecular docking technique. Ethnomedicinal data collected from 185 informants were quantitatively analyzed employing eight quantitative indices to highlight the use diversity and most frequently used part of the plant. High scores of certain indices employed, such as Use Value (UV = 0.52), Fidelity Level (FL = 68.42%) and Tissue Importance Value (TIV = 1) clearly illustrate an ethnomedicinal lead regarding medico-nutritional benefits of the tuber part used against intestinal helminthic diseases of veterinary animals. Based on this ethno-guided lead, root tuber has been investigated for its chemical profiling by the estimation of total phenolics, flavonoids, tannins and alkaloids, along with HPLC and GC-MS analyses. Anthelmintic property was evaluated with the tuber extracts by in vitro studies on some helminths of livestock and poultry birds, and it showed promising results against the tested parasites namely Cotylophoron cotylophorum, Raillietina tetragona and Setaria cervi. Toxicity assessments of tuber extract through in vitro and in vivo methods were performed using Vero cells and BALB/c mice. Nontoxic nature of the studied tuber extract was observed even in higher experimental doses. Out of 12 phytocompounds identified by GC-MS analysis, one compound [Morphinan-4,5-epoxy-3,6-di-ol,6- (7-nitrobenzofurazan-4-yl) amino-] exhibited the best binding conformations in cost of the lowest binding energy values with six target proteins that include one anti-inflammatory, one antioxidant, and four anthelmintic proteins. The findings of our study are found very encouraging to evaluate this tuber drug furthermore intensively towards the development of anthelmintic veterinary medicine.

Optimization and Characterization of Phenolic Extraction Conditions and Antioxidant Activity Evaluation of Adenanthera pavonina L. Bark.

The presence of high levels of secondary metabolites in medicinal plants can significantly influence the progress of drug development. Here, we aimed to maximize phenolic extraction from Adenanthera pavonina L. stem bark using various solvents such as ethyl acetate, methanol, petroleum ether, and chloroform. A response surface method (RSM) with a central composite design (CCD) statistical technique was applied to optimize the extraction process, employing three important extracting parameters such as extraction time (h), temperature (°C), and solvent composition (% v/v of methanol/water) to obtain the highest phenolic content. Total phenolic content (TPC) and antioxidant activity (IC50 of extract's DPPH radical scavenging activity) were used as response variables to find the influence of these extracting parameters. Among the various solvents used, methanol extract showed the highest contents of phenolics and the maximum level of antioxidant activity with a lower IC50 value. The notable TPC and IC50 value of the extract's DPPH radical scavenging capacity were found to be 181.69 ± 0.20 mg GAE/g dry tissue and 60.13 ± 0.11 mg/mL, respectively, under the optimal conditions with a solvent composition of 71.61% (v/v) of methanol/water, extraction temperature of 42.52 °C, and extraction time of 24 h. The optimized extract of A. pavonina stem bark was further subjected to HPLC analysis, where six phenolic compounds, including coumarin, p-coumaric acid, chlorogenic acid, sinapic acid, gallic acid, and caffeic acid, were identified along with their respective quantities. Overall, the findings of this study uncover a low-cost analytical model for maximizing phenolic extraction from A. pavonina bark with enhanced antioxidant activity.

Phytochemical Profiling, Biological Activities, and In Silico Molecular Docking Studies of Causonis trifolia (L.) Mabb. & J.Wen Shoot.

Causonis trifolia (L.) Mabb. & J.Wen, commonly known as "fox grape", is an ethnomedicinally important twining herb of the Vitaceae family, and it is used by ethnic communities for its wide range of therapeutic properties. Our research aims to investigate the chemical composition; antioxidant, anti-inflammatory, and antidiabetic activities; and mechanisms of interaction between the identified selective chemical compounds and the target proteins associated with antioxidant, anti-inflammatory, and antidiabetic effects of the optimised phenolic extract of Causonis trifolia (L.) Mabb. & J.Wen, shoot (PECTS) to endorse the plant as a potential drug candidate for a future bioprospecting programme. Here, we employed the response surface methodology (RSM) with a Box-Behnken design to enrich the methanolic extract of C. trifolia shoot with phenolic ingredients by optimising three key parameters: solvent concentration (% v/v, methanol:water), extraction temperature (°C), and extraction duration (hours). From the quantitative phytochemical estimation, it was evident that the PECTS contained good amounts of phenolics, flavonoids, tannins, and alkaloids. During the HPLC analysis, we identified a total of eight phenolic and flavonoid compounds (gallic acid, catechin hydrate, chlorogenic acid, caffeic acid, p-coumaric acid, sinapic acid, coumarin, and kaempferol) and quantified their respective contents from the PECTS. The GC-MS analysis of the PECTS highlighted the presence of 19 phytochemicals. In addition, the bioactivity study of the PECTS showed remarkable potentiality as antioxidant, anti-inflammatory, and antidiabetic agents. In silico molecular docking and computational molecular modelling were employed to investigate the anti-inflammatory, antioxidant, and antidiabetic properties of the putative bioactive compounds derived from the PECTS using the GC-MS technique to understand the drug-receptor interactions, including their binding pattern. Out of the 19 phytocompounds identified by the GC-MS analysis, one compound, ergosta-5,22-dien-3-ol, acetate, (3ß,22E), exhibited the best binding conformations with the target proteins involved in anti-inflammatory (e.g., Tnf-α and Cox-2), antioxidant (SOD), and antidiabetic (e.g., α-amylase and aldo reductase) activities. The nontoxic nature of this optimised extract was also evident during the in vitro cell toxicity assay against the Vero cell line and the in vivo acute toxicity study on BALB/c mice. We believe the results of the present study will pave the way for the invention of novel drugs efficacious for several ailments using the C. trifolia plant.

Natural Phytocompounds from Common Indian Spices for Identification of Three Potential Inhibitors of Breast Cancer: A Molecular Modelling Approach.

Breast cancer is the second most common cancer-related cause of death for women throughout the globe. In spite of some effective measures, the main concerns with traditional anti-cancer chemotherapy are its low bioavailability, physical side effects, acquired resistance of cancer cells and non-specific targeting. Now researchers have taken the initiative to establish natural product-based therapy methods and to identify viable hits for future lead optimization in the development of breast cancer medication. Our study aims to identify the potent phytocompounds from five very popular Indian spices (Zingiber officinale Roscoe, Cuminum cyminum L., Piper nigrum L., Curcuma longa L., and Allium sativum L.). From these spices, a total of 200 phytocompounds were identified and screened against three target genes, namely, cyclin-dependent kinase 8 (CDK 8), progesterone receptor (PR) and epidermal growth factor receptor (EGFR), through structure-based virtual screening using iGEMDOCK 2.1 software. Based on the binding affinity score, the top three phytocompounds against each target protein (cynaroside (-149.66 Kcal/mol), apigetrin (-139.527 Kcal/mol) and curcumin (-138.149 Kcal/mol) against CDK8; apigetrin (-123.298 Kcal/mol), cynaroside (-118.635 Kcal/mol) and xyloglucan (-113.788 Kcal/mol) against PR; cynaroside (-119.18 Kcal/mol), apigetrin (-105.185 Kcal/mol) and xyloglucan (-105.106 Kcal/mol) against EGFR) were selected. Apigetrin, cynaroside, curcumin, and xyloglucan were finally identified for further docking analysis with the respective three target proteins. Autodock 4.2 was applied to screen the optimal binding position and to assess the relative intensity of binding interactions. In addition, the ADME/T property checks and bioactivity scores analysis of were performed to understand the suitability of these four phytocompounds to be potential candidates for developing effective and non-toxic anticancer agents. Based on this in silico analysis, we believe this study could contribute to current efforts to develop new drugs for treating breast cancer.

A comprehensive and systematic review on potential anticancer activities of eugenol: From pre-clinical evidence to molecular mechanisms of action.

BACKGROUND: Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is an important simple phenolic compound mainly derived from Syzygium aromaticum and many other plants. It is traditionally used in ayurveda and aromatherapy for the healing of many health problems. It also has significant applications in dentistry, agriculture, and flavour industry. This simple phenol has an eclectic range of pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. It is regarded as safe by the Food and Agricultural Organization of the United Nations due to its non-carcinogenic and non-mutagenic properties. PURPOSE: The aim of this comprehensive review is to present a critical and systematic assessment of the antitumor ability of eugenol and its associated molecular targets in various cancers. METHODS: It was carried out following the preferred reporting items for systematic reviews and meta-analysis guidelines. Risk of bias assessment was performed using the SYstematic review centre for laboratory animal experimentation guidelines. The literature search was performed in standard databases such as Science Direct, PubMed, Google Scholar, Scopus, and Web of Science using the keywords 'eugenol' or 'eugenol essential oil' and 'anti-cancer properties of eugenol'. RESULTS: The scientific information from fifty-three studies was encompassed in the present review work. Eugenol exhibits significant anticancer effects in a variety of biological pathways, namely apoptosis, autophagy, cell cycle progression, inflammation, invasion, and metastasis. Eugenol-induced apoptosis has been noticed in osteosarcoma, skin tumors, melanoma, leukemia, gastric and mast cells. It decreases the expression of cyclin D1, cyclin B, proliferating cell nuclear antigen, nuclear factor-ƙB, inhibitor of nuclear factor ƙB, and B-cell lymphoma-2. Eugenol increases the expression of B-cell lymphoma-2 (BCL-2) associated X, BH3-interacting domain death agonist, BCL-2 associated agonist of cell death, apoptotic protease activating factor 1, cytochrome c, p21, and p53. CONCLUSION: The anticancer potential exhibited by eugenol is mainly attributed to its anti-metastatic, anti-proliferative, anti-angiogenic, anti-inflammatory, cell cycle arrest, apoptotic, and autophagic effects. Hence, the use of eugenol alone or along with other chemotherapeutic anticancer agents is found to be very effective in cancer therapy.

Inventorization and Consensus Analysis of Ethnoveterinary Medicinal Knowledge Among the Local People in Eastern India: Perception, Cultural Significance, and Resilience.

Livestock is the main backbone of the rural economy of an agriculture-based country like India. To mitigate the economic loss due to livestock's poor performance and illness, folk phytotherapy for livestock healthcare is still actively practiced in India. Literature survey revealed that the laterite region of eastern India, characterized by its cultural, ethnic, and biological diversities, as well as topographical uniqueness, lacks comprehensive information on ethnoveterinary medicinal knowledge. The objective of the present study includes documentation of traditional knowledge of ethnoveterinary medicine (EVM) from the northern laterite region in eastern India. Ethnoveterinary medicinal data were collected using a semi-structured questionnaire, free listing, and focus group discussions. The factor for informants' consensus (Fic), fidelity level (FL), and cultural value (CV) index have been employed for quantitative analyses. Jaccard index (JI) was used to check the knowledge similarity. Altogether, 1,234 citations were made by 132 participants. In total, 232 recorded ethnomedicinal species are used for preparing 306 remedies to treat 79 health disorders of livestock. Recorded species are distributed in 92 families, and Fabaceae is identified as the most medicinally diversified. Uses of 24 angiospermic taxa, one pteridophyte, and two fungal species were exclusively new to the existing inventory of Indian traditional ethnoveterinary medicine. In 20 disease categories, the informant consensus (Fic) value ranges from 0.4 to 0.83. According to the FL value and use-mention factor, 23 EVM plants have been identified as the most important species in the respective disease categories. Value of CV index highlighted nine species as culturally most significant (CV ≥ 0.0025 and frequency of citation ≥20) in the laterite region of eastern India. A large extent of recorded data are quite worthy for the Indian folk veterinary medicinal repository. A handful of new data reported here and statistically justified culturally most significant species will provide the golden opportunity for bioprospecting research.

Polyphenol enriched ethanolic extract of Cajanus scarabaeoides (L.) Thouars exerts potential antifilarial activity by inducing oxidative stress and programmed cell death.

Development of antifilarial drug from the natural sources is considered as one of the most efficacious, safe, and affordable approaches. In this study, we report the antifilarial activity of a leguminous plant Cajanus scarabaeoides (L.) Thouars. The polyphenol-rich ethanolic extract obtained from the stem part of the plant C. scarabaeoides (EECs) was found to be efficient in killing the filarial nematode Setaria cervi in all the three developmental stages viz. oocytes, microfilariae (Mf) and adults with LD50 values of 2.5, 10 and 35 µg/ml, respectively. While studying the molecular mechanism of action, we found that induction of oxidative stress plays the key role in inducing the mortality in S. cervi. The redox imbalance finally results in activation of the nematode CED pathway that executes the death of the parasite. Intriguingly, EECs was found to be selectively active against the worm and absolutely non-toxic to the mammalian cells and tissues. Taken together, our experimental data demonstrate that C. scarabaeoides can be chosen as an affordable natural therapeutic for treating filarial infection in the future with high efficacy and less toxicity.