Bioeconomy and ethnopharmacology - Translational perspective and sustainability of the bioresources of northeast region of India.

ETHNOPHARMACOLOGICAL RELEVANCE: The ecological environment of Northeast region of India (NER), with its high humidity, has resulted in greater speciation and genetic diversity of plant, animal, and microbial species. This region is not only rich in ethnic and cultural diversity, but it is also a major biodiversity hotspot. The sustainable use of these bioresources can contribute to the region's bioeconomic development. AIM OF THE STUDY: The review aimed to deliver various perspectives on the development of bioeconomy from NER bioresources under the tenets of sustainable utilization and socioeconomic expansion. MATERIALS AND METHODS: Relevant information related to prospects of the approaches and techniques pertaining to the sustainable use of ethnomedicine resources for the growth of the bioeconomy were retrieved from PubMed, ScienceDirect, Google Scholar, Scopus, and Springer from 1984 to 2023. All the appropriate abstracts, full-text articles and various book chapters on bioeconomy and ethnopharmacology were conferred. RESULT: As the population grows, so does the demand for basic necessities such as food, health, and energy resources, where insufficient resource utilization and unsustainable pattern of material consumption cause impediments to economic development. On the other hand, the bioeconomy concept leads to "the production of renewable biological resources and the conversion of these resources and waste streams into value-added products. CONCLUSIONS: In this context, major emphasis should be placed on strengthening the economy's backbone in order to ensure sustainable use of these resources and livelihood security; in other words, it can boost the bio-economy by empowering the local people in general.

A Validated High-Performance Thin-Layer Chromatography Technique for Routine Analysis of Curcumin in Four Different Species of Curcuma Viz. C. amada, C. caesia, C. longa and C. zedoaria.

In this study, we investigated a new, simple, sensitive, selective and precise high-performance thin-layer chromatography (HPTLC) fingerprint and quantitative estimation method for the routine analysis of curcumin in Curcuma species viz. Curcuma amada, Curcuma caesia, Curcuma longa and Curcuma zedoaria. Linear ascending development was carried out in a twin-trough glass chamber saturated with toluene:acetic acid (4:1; v/v with 20 minutes of saturation). The plate was dried and analyzed by CAMAG TLC scanner III at white light and 366 nm. The system was found to give compact spots for curcumin (Rf 0.42). The relationship between the concentration of standard solutions and the peak response is linear within the concentration range of 10-70 ng/spot for curcumin. In result, curcumin was not detected in any of C. caesia extracts. The percentage of curcumin was found between 0.042 and 4.908 (%w/w) in different Curcuma species obtained by two different extraction methods viz. Soxhlet and sonication, respectively. Further, extraction via Soxhlet method is most suitable method to get higher curcumin content from rhizomes. The proposed HPTLC method may be use for routine quality testing and quantification of curcumin in Curcuma samples.

Therapeutic Potential of Myricetin in the Treatment of Neurological, Neuropsychiatric, and Neurodegenerative Disorders.

Myricetin (MC), 3,5,7,3',4',5'-hexahydroxyflavone, chemically belongs to a flavonoid category known to confer antioxidant, antimicrobial, antidiabetic, and neuroprotective effects. MC is known to suppress the generation of Reactive Oxygen Species (ROS), lipid peroxidation (MDA), and inflammatory markers. It has been reported to improve insulin function in the human brain and periphery. Besides this, it modulates several neurochemicals including glutamate, GABA, serotonin, etc. MC has been shown to reduce the expression of the enzyme Mono Amine Oxidase (MAO), which is responsible for the metabolism of monoamines. MC treatment reduces levels of plasma corticosterone and restores hippocampal BDNF (full form) protein in stressed animals. Further, MC has shown its protective effect against amyloid-beta, MPTP, rotenone, 6-OHDA, etc. suggesting its potential role against neurodegenerative disorders. The aim of the present review is to highlight the therapeutic potential of MC in the treatment of several neurological, neuropsychiatric, and neurodegenerative disorders.

Ageratina adenophora (Spreng.) King & H. Rob. Standardized leaf extract as an antidiabetic agent for type 2 diabetes: An in vitro and in vivo evaluation.

Type 2 diabetes has become one of the major health concerns of the 21st century, marked by hyperglycemia or glycosuria, and is associated with the development of several secondary health complications. Due to the fact that chemically synthesized drugs lead to several inevitable side effects, new antidiabetic medications from plants have gained substantial attention. Thus, the current study aims to evaluate the antidiabetic capacity of the Ageratina adenophora hydroalcoholic (AAHY) extract in streptozotocin-nicotinamide (STZ-NA)-induced diabetic Wistar albino rats. The rats were segregated randomly into five groups with six rats each. Group I was normal control, and the other four groups were STZ-NA-induced. Group II was designated diabetic control, and group III, IV, and V received metformin (150 mg/kg b.w.) and AAHY extract (200 and 400 mg/kg b.w.) for 28 days. Fasting blood glucose, serum biochemicals, liver and kidney antioxidant parameters, and pancreatic histopathology were observed after the experimental design. The study concludes that the AAHY extract has a significant blood glucose lowering capacity on normoglycemic (87.01 ± 0.54 to 57.21 ± 0.31), diabetic (324 ± 2.94 to 93 ± 2.04), and oral glucose-loaded (117.75 ± 3.35 to 92.75 ± 2.09) Wistar albino rats. The in vitro studies show that the AAHY extract has α-glucosidase and α-amylase inhibitory activities which can restore the altered blood glucose level, glycated hemoglobin, body weight, and serum enzymes such as serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, serum alkaline phosphatase, total protein, urea, and creatinine levels close to the normal range in the treated STZ-NA-induced diabetic rats. The evaluation of these serum biochemicals is crucial for monitoring the diabetic condition. The AAHY extract has significantly enhanced tissue antioxidant parameters, such as superoxide dismutase, glutathione, and lipid peroxidation, close to normal levels. The presence of high-quantity chlorogenic (6.47% w/w) and caffeic (3.28% w/w) acids as some of the major phytoconstituents may contribute to the improvement of insulin resistance and oxidative stress. The study provides scientific support for the utilization of A. adenophora to treat type 2 diabetes in the STZ-NA-induced diabetic rat model. Although the preventive role of the AAHY extract in treating Wistar albino rat models against type 2 diabetes mellitus is undeniable, further elaborative research is required for efficacy and safety assessment in human beings.

Chemical Profiling and Therapeutic Evaluation of Standardized Hydroalcoholic Extracts of Terminalia chebula Fruits Collected from Different Locations in Manipur against Colorectal Cancer.

Terminalia chebula Retz. (Fam. Combretaceae), locally called Manahei, is a well-known medicinal plant that grows wildly in Manipur, a Northeastern state of India. It is used as a mild laxative, an anti-inflammatory agent, and a remedy for piles, colds, and ulcers by ethnic communities of the state. The hydroalcoholic extract obtained from four fruit samples of T. chebula collected from different locations in Manipur were analyzed using gas chromatography-mass spectrometry (GC-MS) and high-performance thin-layer chromatography (HPTLC) for their chemical constituents and evaluated for their anticancer activity against the colon cancer cell HCT 116. GC-MS analysis results indicated significant variation in the composition and percentage of major compounds present in the extracts. 1,2,3-Benzenetriol was the most abundant chemical constituent present in all four extracts of T. chebula, ranging from 20.95 to 43.56%. 2-Cyclopenten-1-one, 5-hydroxymethylfurfural, and catechol were commonly present in all extracts. Two marker compounds, gallic acid and ellagic acid, were also quantified usingHPTLC in all four extracts of T. chebula. The highest content of gallic acid (22.44 ± 0.056 µg/mg of dried extract) was observed in TCH, and that of ellagic acidwas found in TYH (11.265 ± 0.089 µg/mg of dried extract). The IC50 value of TYH for the DPPH and ABTS assays (12.16 ± 0.42 and 7.80 ± 0.23 µg/mL) was found to be even lower than that of Trolox (18 ± 0.44 and 10.15 ± 0.24 µg/mL), indicating its strong antioxidant properties among the four extracts of T. chebula. The MTT assay determined the effect of T. chebula extracts on the viability of HCT 116 cells. TYH showed the highest activity with anIC50 value of 52.42 ± 0.87 µg/mL, while the lowest activity was observed in TCH (172.05 ± 2.0 µg/mL). The LDH assay confirmed the cytotoxic effect of TYH in HCT 116 cells. TYH was also found to induce caspase-dependent apoptosis in HCT 116 cells after 48 h of treatment. Our study provides insight into the diversity of T. chebula in Manipur and its potential activity against colon cancer.

6-Gingerol contents of several ginger varieties of Northeast India and correlation of their antioxidant activity in respect to phenolics and flavonoids contents.

INTRODUCTION: Ginger constitutes the rhizome part of the plant Zingiber officinale from the Zingiberaceae family. A large number of ginger varieties with high sensorial and functional quality are found in Northeast India. Hence, phytopharmacological screening of different ginger varieties is essential that will serve as a guideline in applied research to develop high-end products and improve economical margins. OBJECTIVE: To determine the variation in total phenolics content (TPC), total flavonoids content (TFC), and antioxidant activities and correlate that with 6-gingerol contents of different ginger varieties collected from Northeast India using Pearson's correlation analysis. MATERIALS AND METHODS: The TPC and TFC values were determined using standard methods. Antioxidant activities were measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging assays, while reversed-phase high-performance liquid chromatography (RP-HPLC) analysis was utilised for quantitative determination of 6-gingerol content. RESULTS: The result revealed that ginger variety 6 (GV6) contains the highest 6-gingerol content and TPC value showing maximum antioxidant activity, followed by GV5, GV4, GV9, GV3, GV2, GV8, GV1, and GV7. The findings also suggested that the antioxidant activity has much better correlations with TPC as compared with TFC values. Pearson's correlation analysis showed a significant correlation between 6-gingerol contents and TPC values. CONCLUSION: This work underlines the importance of ginger varieties from Northeast India as a source of natural antioxidants with health benefits.

The African cherry: A review of the botany, traditional uses, phytochemistry, and biological activities of Prunus africana (Hook.f.) Kalkman.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunus africana (Hook.f.) Kalkman (Rosaceae), commonly known as "Pygeum" or "African cherry", occurs in mainland montane forests scattered across sub-Saharan Africa, Madagascar, and some surrounding islands. Traditionally, decoctions of the stem-bark are taken orally for the treatment of a wide variety of conditions, such as benign prostatic hyperplasia (BPH), stomach ache, chest pain, malaria, heart conditions, and gonorrhoea, as well as urinary and kidney diseases. The timber is used to make axe handles and for other household needs. The dense wood is also sawn for timber. AIM: The fragmented information available on the ethnobotany, phytochemistry, and biological activities of the medicinally important P. africana was collated, organised, and analysed in this review, to highlight knowledge voids that can be addressed through future research. MATERIALS AND METHODS: A bibliometric analysis of research output on P. africana was conducted on literature retrieved, using the Scopus® database. The trend in the publications over time was assessed and a network analysis of collaborations between countries and authors was carried out. Furthermore, a detailed review of the literature over the period 1971 to 2021, acquired through Scopus, ScienceDirect, SciFinder, Pubmed, Scirp, DOAJ and Google Scholar, was conducted. All relevant abstracts, full-text articles and various book chapters on the botanical and ethnopharmacological aspects of P. africana, written in English and German, were consulted. RESULTS: A total of 455 documents published from 1971 to 2021, were retrieved using the Scopus search. Analysis of the data showed that the majority of these documents were original research articles, followed by reviews and lastly a miscellaneous group comprising conference papers, book chapters, short surveys, editorials and letters. Data were analysed for annual output and areas of intense research focus, and countries with high research output, productive institutions and authors, and collaborative networks were identified. Prunus africana is reported to exhibit anti-inflammatory, analgesic, antimicrobial, anti-oxidant, antiviral, antimutagenic, anti-asthmatic, anti-androgenic, antiproliferative and apoptotic activities amongst others. Phytosterols and other secondary metabolites such as phenols, triterpenes, fatty acids, and linear alcohols have been the focus of phytochemical investigations. The biological activity has largely been ascribed to the phytosterols (mainly 3-ß-sitosterol, 3-ß-sitostenone, and 3-ß-sitosterol-glucoside), which inhibit the production of prostaglandins in the prostate, thereby suppressing the inflammatory symptoms associated with BPH and chronic prostatitis. CONCLUSIONS: Many of the ethnobotanical assertions for the biological activity of P. africana have been confirmed through in vitro and in vivo studies. However, a disparity exists between the biological activity of the whole extract and that of single compounds isolated from the extract, which were reported to be less effective. This finding suggests that a different approach to biological activity studies should be encouraged that takes all secondary metabolites present into consideration. A robust technique, such as multivariate biochemometric data analysis, which allows for a holistic intervention to study the biological activity of a species is suggested. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products to replace the time-consuming and laborious methods currently in use.

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

Background: Glycyrrhiza glabra L. (G. glabra) commonly known as liquorice is one of the highly exploited and utilized medicinal plant of the world. Since ancient times liquorice is considered as an auspicious and valuable traditional medicine across the world for treatment of various ailments. Method: Several electronic online scientific databases such as Science Direct, PubMed, Scopus, Scifinder, Google Scholar, online books and reports were assessed for collecting information. All the collected information was classified into different sections to meet the objective of the paper. Results: The electronic database search yielded 3908 articles from different countries. Out of them one ninety-eight articles published between 1956 and 2021 were included, corresponding to all detailed review on G. glabra and research on anti-inflammatories, antivirals and immunomodulatory through pre-clinical and clinical models. From all selective area of studies on G. glabra and its bioactive components it was established (including molecular mechanisms) as a suitable remedy as per the current requirement of pandemic situation arise through respiratory tract infection. Conclusion: Different relevant studies have been thoroughly reviewed to gain an insight on utility of liquorice and its bioactive constituents for anti-inflammatories, antivirals and immunomodulatory effects with special emphasized for prevention and treatment of COVID-19 infection with possible mechanism of action at molecular level. Proposed directions for future research are also outlined to encourage researchers to find out various mechanistic targets and useful value added products of liquorice in future investigations.

Cannabis Sativa L. Flower and Bud Extracts Inhibited In vitro Cholinesterases and ß-Secretase Enzymes Activities: Possible Mechanisms of Cannabis Use in Alzheimer Disease.

BACKGROUND: There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer's disease, but there is a lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer's disease. AIM: The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and ß-secretase enzymes activities as one of the possible mechanisms of Alzheimer's disease. METHODS: The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and ß-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high-performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts. RESULTS: Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards ß-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure. CONCLUSION: Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.

Therapeutic Potential of Phytoconstituents in Management of Alzheimer's Disease.

Since primitive times, herbs have been extensively used in conventional remedies for boosting cognitive impairment and age-associated memory loss. It is mentioned that medicinal plants have a variety of dynamic components, and they have become a prominent choice for synthetic medications for the care of cognitive and associated disorders. Herbal remedies have played a major role in the progression of medicine, and many advanced drugs have already been developed. Many studies have endorsed practicing herbal remedies with phytoconstituents, for healing Alzheimer's disease (AD). All the information in this article was collated from selected research papers from online scientific databases, such as PubMed, Web of Science, and Scopus. The aim of this article is to convey the potential of herbal remedies for the prospect management of Alzheimer's and related diseases. Herbal remedies may be useful in the discovery and advancement of drugs, thus extending new leads for neurodegenerative diseases such as AD. Nanocarriers play a significant role in delivering herbal medicaments to a specific target. Therefore, many drugs have been described for the management of age-linked complaints such as dementia, AD, and the like. Several phytochemicals are capable of managing AD, but their therapeutic claims are restricted due to their lower solubility and metabolism. These limitations of natural therapeutics can be overcome by using a targeted nanocarrier system. This article will provide the primitive remedies as well as the development of herbal remedies for AD management.

Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective.

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.

Traditional uses, phytochemistry and pharmacological attributes of Pterocarpus santalinus and future directions: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterocarpus santalinus, an ancient folk medicine, is endemic to the eastern ghats of south India, and the heartwood is prescribed since time immemorial for the mitigation of inflammatory disorders in traditional practice and ayurvedic system of medicines. AIM OF THE STUDY: This review aims to provide collective pieces of information of the traditional uses, phytochemicals, and pharmacological facets of P. santalinus, with an intuition for promoting future research to explore its pharmaceutical potential as a therapeutic agent against modern maladies. MATERIAL AND METHODS: Extensive literature search was performed to collate the data by using various electronic search engines. A network pharmacology-based approach is incorporated for validation of traditional claims orbiting around anti-inflammatory properties and directed its future exploration against obesity, ovarian inflammation, ovarian folliculogenesis, and inflammatory breast cancer. RESULTS: In a nutshell, the present review encompasses the phytochemistry, pharmacology of this species intending to sensitize the scientific community for future research on this promising plant. Nearly 85 chemical constituents are reported from the plants wherein bark and leaves are enriched with the lupane and oleanane class of triterpene while sesquiterpenes and polyphenolic compounds are predominantly present in the heartwood of the plant. Although phytochemical investigations are being reported since the mid-twentieth century however there has been recent interest in the evaluation of biological activities such as anti-inflammatory, anti-oxidant, anti-cancer, anti-viral, etc. CONCLUSION: In conclusion, a systematic phytochemical analysis and pharmacological exploration in close collaboration for establishing the therapeutic potential of the chemical constituents present in P. santalinus is recommended to substantiate the traditional claims for bringing it into the mainstream pharmaceutical and commercial utilization.

Therapeutic potential of mangiferin in the treatment of various neuropsychiatric and neurodegenerative disorders.

Xanthones are important chemical class of bioactive products that confers therapeutic benefits. Of several xanthones, mangiferin is known to be distributed widely across several fruits, vegetables and medicinal plants. Mangiferin has been shown to exert neuroprotective effects in both in-vitro and in-vivo models. Mangiferin attenuates cerebral infarction, cerebral edema, lipid peroxidation (MDA), neuronal damage, etc. Mangiferin further potentiate levels of endogenous antioxidants to confer protection against the oxidative stress inside the neurons. Mangiferin is involved in the regulation of various signaling pathways that influences the production and levels of proinflammatory cytokines in brain. Mangiferin cosunteracted the neurotoxic effect of amyloid-beta, MPTP, rotenone, 6-OHDA etc and confer protection to neurons. These evidence suggested that the mangiferin may be a potential therapeutic strategy for the treatment of various neurological disorders. The present review demonstrated the pharmacodynamics-pharmacokinetics of mangiferin and neurotherapeutic potential in several neurological disorders with underlying mechanisms.

Potential Leads from Liquorice Against SARS-CoV-2 Main Protease using Molecular Docking Simulation Studies.

AIM AND OBJECTIVE: At present, the world is facing a global pandemic threat of SARSCoV- 2 or COVID-19 and to date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine, in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. MATERIALS AND METHODS: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (Mpro) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 Mpro as a target protein having PDB ID: 6LU7. RESULTS: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards Mpro representing the binding energy of -8.6 and -7.9 Kcal/mol, respectively. Nevertheless, the other four compounds were also quite comparable with the later one. CONCLUSION: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

Acute and sub-chronic toxicity studies of Benincasa hispida (Thunb.) cogniaux fruit extract in rodents.

The objective of the present study was to evaluate the safety of standardized 70% ethanolic extract of Benincasa hispida fruit pulp (HABH) in rodents. Chemical characterization of HABH has been done by GC-MS and dimethylsulfoxonium formyl methylide, l-(+)-ascorbic acid and 2,6-dihexadecanoate were identified as major compounds in the extract. Acute oral toxicity study of HABH was done according to the Organization for Economic Cooperation and Development (OECD) guideline, by 'up and down' method, using the limit test at 2000 mg/kg, body weight in mice and were observed up to 14 days. In sub-chronic oral toxicity study, HABH was administered to Wistar rats at doses of 1000, 200 and 40 mg/kg b. w. per day for 90 days. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the limit test dose level (2000 mg/kg b. w.). In sub-chronic oral toxicity study, there was no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical and urine analysis revealed the non-adverse effects of prolonged oral consumption of HABH. The histopathologic examination did not show any differences in vital organs. Based on our findings, HABH, at dosage levels up to 1000 mg/kg b. w., is non-toxic and safe for long term oral consumption.

Structure-Based Screening of DNA GyraseB Inhibitors for Therapeutic Applications in Tuberculosis: a Pharmacoinformatics Study.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) and considered as serious public health concern worldwide which kills approximately five thousand people every day. Therefore, TB drug development efforts are in gigantic need for identification of new potential chemical agents to eradicate TB from the society. The bacterial DNA gyrase B (GyrB) protein as an experimentally widely accepted effective drug target for the development of TB chemotherapeutics. In the present study, advanced pharmacoinformatics approaches were used to screen the Mcule database against the GyrB protein. Based on a number of chemometric parameters, five molecules were found to be crucial to inhibit the GyrB. A number of molecular binding interactions between the proposed inhibitors and important active site residues of GyrB were observed. The predicted drug-likeness properties of all molecules were indicated that compounds possess characteristics to be the drug-like candidates. The dynamic nature of each molecule was explored through the molecular dynamics (MD) simulation study. Various analyzing parameters from MD simulation trajectory have suggested rationality of the molecules to be potential GyrB inhibitor. Moreover, the binding free energy was calculated from the entire MD simulation trajectories highlighted greater binding free energy values for all newly identified compounds also substantiated the strong binding affection towards the GyrB in comparison to the novobiocin. Therefore, the proposed molecules might be considered as potential anti-TB chemical agents for future drug discovery purposes subjected to experimental validation. Graphical Abstract.

Isolation, in vitro evaluation and molecular docking of acetylcholinesterase inhibitors from South African Amaryllidaceae.

Inhibition of acetylcholinesterase (AChE) is considered a promising strategy for the treatment of Alzheimer's disease (AD) and dementia. Members of the Amaryllidaceae family are well known for their pharmacologically active alkaloids, including galanthamine, which is used to treat AD. The aim of this study was to evaluate the potential of South African Amaryllidaceae species to inhibit AChE, to isolate the active compounds, and probe their ability to bind the enzyme using molecular docking. The AChE inhibitory activity of extracts of 41 samples, representing 14 genera and 28 species, as well as isolated compounds, were evaluated in vitro using a qualitative thin layer chromatography (TLC) bio-autography assay and Ellman's method in a quantitative 96-well microplate assay. Targeted isolation of compounds was achieved with the aid of preparative-high perfomance liquid chromatography-mass spectrometry. The structures of the isolates were elucidated using nuclear magnetic resonance spectrocopy, and were docked into the active site of AChE to rationalise their biological activities. The most active species were found to be Amaryllis belladonna L (IC50 14.3 ± 2.6 µg/mL), Nerine huttoniae Schönland (IC50 45.3 ± 0.4 µg/mL) and Nerine undulata (L.) Herb. (IC50 52.8 ± 0.5 µg/mL), while TLC bio-autography indicated the presence of several active compounds in the methanol extracts. Four compounds, isolated from A. belladonna, were identified as belladine, undulatine, buphanidrine and acetylcaranine. Acetylcaranine and undulatine were previously isolated from A. belladonna, while belladine and buphanidrine were reported from other South African Amaryllidaceae species. Using Ellman's method, acetylcaranine was found to be the most active of the isolates towards AChE, with an IC50 of 11.7 ± 0.7 µM, comparable to that of galanthamine (IC50 = 6.19 ± 2.60 µM). Molecular docking successfully predicted the binding modes of ligands within receptor binding sites. Acetylcaranine was predicted by the docking workflow to have the highest activity, which corresponds to the in vitro results. Both qualitative and quantitative assays indicate that several South African Amaryllidaceae species are notable AChE inhibitors.

Evaluation of the nutritional composition of Myrothamnus flabellifolius (Welw.) herbal tea and its protective effect against oxidative hepatic cell injury.

The nutrient composition of Myrothamnus flabellifolius leaf tea extract (MLTE) and its protective effect against oxidative hepatic cell injury were evaluated. Gallic acid, caffeic acid, ferulic acid, methyl gallate, and epicatechin were identified in MLTE by high-performance liquid chromatography (HPLC). The tea extract showed an appreciable nutritional content of proximate, sugar, vitamin E, monounsaturated fatty acids, omega 6 and 9 unsaturated fatty acids, as well as considerable amounts of various mineral elements. Nineteen amino acids were found. Moreover, MLTE exhibited potent in vitro antioxidant activities, presumably because of its richness in polyphenols (gallic acid and ferulic acid) and vitamin E. In Chang liver cells, pretreatment with MLTE suppressed oxidative lipid peroxidation (IC50  = 113.11 µg/ml) and GSH depletion (IC50  = 70.49 µg/ml) without causing cytotoxicity. These data support the local consumption of M. flabellifolius herbal tea, which may be used against oxidative stress-induced diseases while providing the body with necessary nutrients. PRACTICAL APPLICATION: Herbal teas are one of the most consumed beverages in the world today, due to their refreshing taste and additional health benefits. Myrothamnus flabellifolius herbal tea is a widely used traditional herbal tea in Southern Africa with potentials for commercialization due to its pleasant flavor. This study, for the first time, reported the nutritional composition of the leaf decoction of M. flabellifolius and its protective effect on hepatic oxidative insults. These results can inform the dietary and nutritional use of the tea for optimum benefits, as well as provide preliminary scientific validation of the use of the herbal tea as an antioxidant beverage with good nutritional value.

Exploring Common Culinary Herbs and Spices as Potential Anti-Quorum Sensing Agents.

Quorum sensing controls bacterial pathogenesis and virulence; hence, interrupting this system renders pathogenic bacteria non-virulent, and presents a novel treatment for various bacterial infections. In the search for novel anti-quorum sensing (AQS) compounds, 14 common culinary herbs and spices were screened for potential antipathogenicity activity against Chromobacterium violaceum ATCC 12472. Extracts of Glycyrrhiza glabra (liquorice), Apium graveolens (celery), Capsicum annuum (cayenne pepper) and Syzygium anisatum (aniseed) demonstrated good AQS potential, yielding opaque halo zones ranging from 12⁻19 mm diameter at sub-minimum inhibitory concentrations (0.350⁻4.00 mg/mL). For the same species, the percentage reduction in violacein production ranged from 56.4 to 97.3%. Zones with violacein inhibitory effects were evident in a celery extract analysed using high performance thin layer chromatography-bio-autography. The major active compound was isolated from celery using preparative-high performance liquid chromatography-mass spectrometry and identified using gas chromatography-mass spectrometry (GC-MS) as 3-n-butyl-4,5-dihydrophthalide (sedanenolide). Potent opaque zones of inhibition observed on the HPTLC-bio-autography plate seeded with C. violaceum confirmed that sedanenolide was probably largely responsible for the AQS activity of celery. The bacteriocidal properties of many herbs and spices are reported. This study, however, was focussed on AQS activity, and may serve as initial scientific validation for the anti-infective properties ascribed to several culinary herbs and spices.

Identification, Isolation and Determination of Biomarkers for Quality Control of Bush Tea (Athrixia phyllicoides).

Athrixia phylicoides, known as "bush tea", grows abundantly in South Africa. An infusion of the leaves is used as a beverage and to treat a multitude of health conditions. The aim of this study was to investigate the chemical variation within A. phylicoides and to identify characteristic compounds for quality control. Samples from 12 locations in South Africa were analysed using ultra-performance liquid chromatography. Hierarchical cluster analysis of the aligned ultra-performance liquid chromatography-time-of-flight mass spectrometry data indicated two groups on the resulting dendrogram, representing 48 samples. Five marker compounds, identified through visual inspection and the construction of a discriminant analysis model, were evident on the ultra-performance liquid chromatography-MS profiles. Four of these compounds were isolated and identified, three as hydroxy methoxyflavones and the fourth as a coumarate, using nuclear magnetic resonance spectroscopy. An ultra-performance liquid chromatography-photodiode array method was developed and validated for the determination of the marker compounds using the isolates as standards. The limits of detection for the four compounds ranged from 0.92 - 2.50 µg/mL. Their recoveries at three concentration levels (1.00, 10.0, and 100 µg/mL) were between 97.0 and 101%, while acceptable intra- and inter-day precision was obtained as reflected by percentage relative standard deviation values below 2.24%. The concentrations of all the marker compounds were found to be higher in samples corresponding to Group 1 of the dendrogram than in those from Group 2. This may be attributable to differences in altitude, climate, and some edaphic factors. Identification of these marker compounds will make a valuable contribution towards the quality control and sustainable commercialisation of bush tea.