Investigation of Antioxidant Activity, Myco-Chemical Content, and GC-MS Based Molecular Docking Analysis of Bioactive Chemicals from Amanita konajensis (Agaricomycetes), a Tribal Myco-Food from India.

In humans, a wide range of health disorders have been induced due to an imbalanced metabolism and an excess generation of reactive oxygen species (ROS). Different biological properties found in mushrooms seem to be the reason for their customary use as a favourite delicacy. Therefore, exploration of wild edible mushrooms as a source of various biological compounds is gaining much importance today. Amanita konajensis, one of the underutilized macrofungi popularly consumed in Eastern India, demands a systematic study of its medicinal values. The study aims to explore the myco-chemical contents of A. konajensis ethanolic extract (EtAK1) and screen their antioxidant potency through various in vitro assays. GC-MS analysis identified the chemical components of EtAK1. Further, structure-based virtual screening of the identified compounds was analysed for drug-like properties and molecular docking with the human p38 MAPK protein, a potent targeting pathway for human lung cancer. The morpho-molecular features proved the authenticity of the collected mushroom. The screening assays showed that EtAK1 was abundant in flavonoids, followed by phenolics, ß-carotene, and lycopene, and had strong antioxidant activity with EC50 values of 640-710 µg/mL. The GC-MS analyses of EtAK1 identified the occurrence of 19 bioactive compounds in the mushroom. In silico analysis revealed that anthraergostatetraenol p-chlorobenzoate, one of the compounds identified, displayed high binding affinity (ΔG = -10.6 kcal/mol) with human p38 MAPK. The outcome of this study will pave the way for the invention of myco-medicine using A. konajensis, which may lead to a novel drug for human lung cancer.

In-silico molecular docking and molecular dynamic simulation of γ-elemene and caryophyllene identified from the essential oil of Kaempferia galanga L. against biofilm forming proteins, CrtM and SarA of Staphylococcus aureus.

Medicinal plants play an important role as antimicrobials by inhibiting various key targets of diverse microorganisms. A major antimicrobial component of plants is its essential oil, which are increasingly being studied for their antimicrobial properties as well as for their potential role in the inhibition of biofilm formation. In the present study, essential oil from Kaempferia galanga L was isolated resulting in the identification of eleven compounds. Of these, two of the compounds, γ-elemene and caryophyllene were found to dock with the target proteins, CrtM and SarA of Staphylococcus aureus, which are essential for the formation of biofilm. γ-elemene demonstrated the best binding affinity with CrtM with binding energy of -8.1 kcal/mol whereas caryophyllene and its derivative isocaryophyllene showed the best binding with SarA with binding energy -6.1 kcal/mol. ADMET study of the compounds also revealed that the compounds are non-toxic and can be used as probable compounds for inhibition of biofilms. Molecular dynamic simulation studies revealed high affinity of binding and stability of the molecules with their targets. PCA analysis helped in identifying the principal motions occurring within a trajectory that are essential in inducing conformational changes.Communicated by Ramaswamy H. Sarma.

Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review.

Centella asiatica is an ethnomedicinal herbaceous species that grows abundantly in tropical and sub-tropical regions of China, India, South-Eastern Asia and Africa. It is a popular nutraceutical that is employed in various forms of clinical and cosmetic treatments. C. asiatica extracts are reported widely in Ayurvedic and Chinese traditional medicine to boost memory, prevent cognitive deficits and improve brain functions. The major bioactive constituents of C. asiatica are the pentacyclic triterpenoid glycosides, asiaticoside and madecassoside, and their corresponding aglycones, asiatic acid and madecassic acid. Asiaticoside and madecassoside have been identified as the marker compounds of C. asiatica in the Chinese Pharmacopoeia and these triterpene compounds offer a wide range of pharmacological properties, including neuroprotective, cardioprotective, hepatoprotective, wound healing, anti-inflammatory, anti-oxidant, anti-allergic, anti-depressant, anxiolytic, antifibrotic, antibacterial, anti-arthritic, anti-tumour and immunomodulatory activities. Asiaticoside and madecassoside are also used extensively in treating skin abnormalities, burn injuries, ischaemia, ulcers, asthma, lupus, psoriasis and scleroderma. Besides medicinal applications, these phytocompounds are considered cosmetically beneficial for their role in anti-ageing, skin hydration, collagen synthesis, UV protection and curing scars. Existing reports and experimental studies on these compounds between 2005 and 2022 have been selectively reviewed in this article to provide a comprehensive overview of the numerous therapeutic advantages of asiaticoside and madecassoside and their potential roles in the medical future.

Mangiferin: the miraculous xanthone with diverse pharmacological properties.

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one) is a bioactive component derived primarily from the mango tree. Belonging to the Xanthone family, its structure allows it to engage with a variety of pharmacological targets. The symmetric linked core of xanthones has a heterogeneous biogenetic background. The carbon atoms are designated in a biochemical order, which reveals the reason of ring A (C1-C4) being referred to as acetate originated, and ring B (C5-C8) is referred to as shikimate originated. The antibacterial, hypocholesterolemic, antiallergic, cardiotonic, antidiabetic, anti-neoplastic, neuroprotective, antioxidant and immunomodulatory properties have all been demonstrated for the secondary metabolite. This study assessed and explained the important medical properties of mangiferin available in published literature, as well as its natural source, biosynthesis, absorption and bioavailability; multiple administration routes; metabolism; nanotechnology for enhanced efficacy of mangiferin and its toxicity, to aid the anticipated on-going potential of mangiferin as a novel diagnostic treatment.

Biotechnological and endophytic-mediated production of centellosides in Centella asiatica.

In vitro culture of a plant cell, tissue and organ is a marvellous, eco-friendly biotechnological strategy for the production of phytochemicals. With the emergence of recent biotechnological tools, genetic engineering is now widely practiced enhancing the quality and quantity of plant metabolites. Triterpenoid saponins especially asiaticoside and madecassoside of Centella asiatica (L.) Urb. are popularly known for their neuroprotective activity. It has become necessary to increase the production of asiaticoside and madecassoside because of their high pharmaceutical and industrial demand. Thus, the review aims to provide efficient biotechnological tools along with proper strategies. This review also included a comparative analysis of various carbon sources and biotic and abiotic elicitors. The vital roles of a variety of plant growth regulators and their combinations have also been evaluated at different in vitro growth stages of Centella asiatica. Selection of explants, direct and callus-mediated organogenesis, root organogenesis, somatic embryogenesis, synthetic seed production etc. are also highlighted in this study. In a nutshell, this review will present the research outcomes of different biotechnological interventions used to increase the yield of triterpenoid saponins in C. asiatica. KEY POINTS: • Critical and updated assessment on in vitro biotechnology in C. asiatica. • In vitro propagation of C. asiatica and elicitation of triterpenoid saponins production. • Methods for mass producing C. asiatica.

Barbaloin: an amazing chemical from the 'wonder plant' with multidimensional pharmacological attributes.

Aloe vera (L.) Burm.f. is nicknamed the 'Miracle plant' or sometimes as the 'Wonder plant'. It is a plant that has been used since ancient times for the innumerable health benefits associated with it. It is one of the important plants that has its use in conventional medicinal treatments. It is a perennial succulent, drought-tolerant member of the family Asphodelaceae. There are scores of properties associated with the plant that help in curing various forms of human ailments. Extracts and gels obtained from plants have been shown to be wonderful healers of different conditions, mainly various skin problems. Also, this plant is popular in the cosmetics industry. The underlying properties of the plant are now mainly associated with the natural phytochemicals present in the plant. Diverse groups of phytoingredients are found in the plant, including various phenolics, amino acids, sugars, vitamins, and different other organic compounds, too. One of the primary ingredients found in the plant is the aloin molecule. It is an anthraquinone derivative and exists as an isomer of Aloin A and Aloin B. Barbaloin belonging to the first group is a glucoside of the aloe-emodin anthrone molecule. Various types of pharmacological properties exhibited by the plant can be attributed to this chemical. Few significant ones are antioxidant, anti-inflammatory, anti-diabetic, anti-cancer, anti-microbial, and anti-viral, along with their different immunity-boosting actions. Recently, molecular coupling studies have also found the role of these molecules as a potential cure against the ongoing COVID-19 disease. This study comprehensively focuses on the numerous pharmacological actions of the primary compound barbaloin obtained from the Aloe vera plant along with the mechanism of action and the potent application of these natural molecules under various conditions.

Therapeutic Potential of Different Natural Products for the Treatment of Alzheimer's Disease.

A high incidence of dementia (60-80%) and a high rate of memory loss are two of the most common symptoms of Alzheimer's disease (AD), which affects the elderly. Researchers have recommended that traditional Chinese medicine (TCM) and Indian medicines can be used to prevent and cure AD. Several studies have linked neuroinflammation linked to amyloid-ß (Aß) deposition in the brain to the pathophysiology of neurodegenerative disorders. As a result, more research is needed to determine the role of inflammation in neurodegeneration. Increased microglial activation, cytokine production, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) all play a role in the inflammatory process of AD. This review focuses on the role of neuroinflammation in neuroprotection and the molecular processes used by diverse natural substances, phytochemicals, and herbal formulations in distinct signaling pathways. Currently, researchers are focusing on pharmacologically active natural compounds with the anti-neuroinflammatory potential, making them a possible contender for treating AD. Furthermore, the researchers investigated the limits of past studies on TCM, Indian Ayurveda, and AD. Numerous studies have been carried out to examine the effects of medicinal whole-plant extracts on AD. Clinical investigations have shown that lignans, flavonoids, tannins, polyphenols, triterpenoids, sterols, and alkaloids have anti-inflammatory, antiamyloidogenic, anticholinesterase, and antioxidant properties. This review summarizes information about numerous medicinal plants and isolated compounds used in the treatment of AD and a list of further references.

QSAR, Molecular Docking, MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads.

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm−multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69−0.87, F = 403.46−292.11, etc., internal validation parameters; Q2LOO = 0.69−0.86, Q2LMO = 0.69−0.86, CCCcv = 0.82−0.93, etc., or external validation parameters Q2F1 = 0.64−0.82, Q2F2 = 0.63−0.82, Q2F3 = 0.65−0.81, R2ext = 0.65−0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.

In vitro anti-HIV and cytotoxic effects of pure compounds isolated from Croton macrostachyus Hochst. Ex Delile.

Croton macrostachyus is an important plant in traditional African medicine, widely utilized to treat a variety of diseases. In Kenya, HIV-infected patients use leaf and root decoctions of the plant as a cure for cough, back pain, bleeding, skin diseases, warts, pneumonia, and wounds. This study aimed to evaluate the anti-HIV activities and cytotoxic effects of extracts and chemical constituents isolated from C. macrostachyus. In our previous study we demonstrated that the hexane, CH2Cl2, ethyl acetate and methanol soluble fractions of a 1:1 v/v/ CH2Cl2/MeOH crude extracts of the leaves and stem bark of C. macrostachyus exhibited potent anti-HIV activities against HIV-1 with IC50 values ranging from 0.02-8.1 µg/mL and cytotoxicity effects against MT-4 cells ranging from IC50 = 0.58-174 µg/mL. Hence, hexane soluble extract of 1:1 v/v/ CH2Cl2/MeOH crude extract of the leaves of C. macrostachyus, that was more potent against HIV-1 at IC50 = 0.02 µg/mL was subjected to column chromatography leading to the isolation of 2-methoxy benzyl benzoate (1), lupenone (2), lupeol acetate (3), betulin (4), lupeol (5), sitosterol (6) and stigmasterol (7). Lupenone (2), lupeol acetate (3) and betulin (4) exhibited anti-HIV-1 inhibition at IC50 = 4.7 nM, 4.3 and 4.5 µg/mL respectively. The results obtained from this study support the potential of C. macrostachyus, as a source of anti-HIV constituents.

Nonlinear molecular dynamics of quercetin in Gynocardia odorata and Diospyros malabarica fruits: Its mechanistic role in hepatoprotection.

Liver performs number of critical physiological functions in human system. Intoxication of liver leads to accumulation of free radicals that eventually cause damage, fibrosis, cirrhosis and cancer. Carbon tetrachloride (CCl4) belongs to hepatotoxin is converted to a highly reactive free radical by cytochrome P450 enzymes that causes liver damage. Plant extracts derived quercetin has substantial role in hepatoprotection. This study highlights the possible mechanism by which quercetin plays significant role in hepatoprotection. HPLC analysis revealed the abundance of quercetin in the fruit extracts of Gynocardia odorata and Diospyros malabarica, were isolated, purified and subjected to liver function analysis on Wistar rats. Post quercetin treatment improved liver function parameters in the hepatotoxic Wistar rats by augmenting bilirubin content, SGOT and SGPT activity. Gene expression profile of quercetin treated rats revealed down regulation of HGF, TIMP1 and MMP2 expressed during CCl4 induction. In silico molecular mechanism prediction suggested that quercetin has a high affinity for cell signaling pathway proteins BCL-2, JAK2 and Cytochrome P450 Cyp2E1, which all play a significant role in CCl4 induced hepatotoxicity. In silico molecular docking and molecular dynamics simulation have shown that quercetin has a plausible affinity for major signaling proteins in liver. MMGBSA studies have revealed high binding of quercetin (ΔG) -41.48±11.02, -43.53±6.55 and -39.89±5.78 kcal/mol, with BCL-2, JAK2 and Cyp2E1, respectively which led to better stability of the quercetin bound protein complexes. Therefore, quercetin can act as potent inhibitor against CCl4 induced hepatic injury by regulating BCL-2, JAK2 and Cyp2E1.

Antihypertensive activity of phytocompounds from selected medicinal plants via inhibition of angiotensin-converting enzyme (ACE) protein: an in-silico approach.

Hypertension has been a significant cause of death due to elevated blood pressure worldwide. The results of molecular docking showed out of selected 40 compounds, chasmanthin (-11.05 kcal/mol), and palmarin (-11.22 kcal/mol) showed strong binding with angiotensin-converting enzyme (ACE) target. The inhibitory action of the selected phytocompounds for ACE protein was also validated by comparing it with the reference drugs, lisinopril (-9.42 kcal/mol), and enalapril (-5.07 kcal/mol). MD simulations study of 100 ns also demonstrated stability of chasmanthin, and palmarin within the active sites of ACE protein. Molecular mechanics generalised born surface area (MMGBSA) analysis of MD trajectories exhibited significant binding of palmarin with ACE (dG Bind= -38.65 ± 2.59 kcal/mol) and chasmanthin (dG Bind= -37.64 ± 2.67 kcal/mol). Drug likeness and pharmacokinetics properties of palmarin and chasmanthin was also found to be permissible, thereby suggesting the use of chasmanthin and palmarin as a novel target inhibitor against ACE protein to combat hypertension.

In Silico Investigation of Phytoconstituents of Medicinal Herb 'Piper Longum' Against SARS-CoV-2 by Molecular Docking and Molecular Dynamics Analysis.

Unavailability of treatment for the SARS-CoV-2 virus has raised concern among the population worldwide. This has led to many attempts to find alternative options to prevent the infection of the disease, including focusing on vaccines and drugs. The use of natural products and herbal extracts can be a better option in beating the virus and boosting up immunity. In the present paper, we have done a systematic in silico study of papain-like protease of COVID-19 virus with the chemical constituents of herbal plant Piper Longum. Screening of the pharmacokinetic properties is done with thirty-two phytoconstituents of Piper Longum which help us in selecting the most active components of the plant. After selection molecular docking is performed with Aristololactam (C17H11NO4), Fargesin (C21H22O6), l-asarinin (C20H18O6), Lignans Machilin F (C20H22O5), Piperundecalidine (C23H29NO3), and Pluviatilol (C20H20O6). Molecular dynamic (MD) is also performed with the inhibitor-receptor complex which suggest significant inhibition and a stable complex of I-Asarinin with PLpro. Docking scores and simulation results suggest that I-Asarinin can act as a potential drug like candidate against COVID-19.

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies.

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.