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Monoamine oxidase (MAO) is capable of catalysing the oxidative deamination of amines and neurotransmitters. MAO plays a pivotal role in maintaining neurotransmitters linked to neurological disorders viz. Alzheimer's disease (AD), Parkinson's disease (PD) etc. Therefore, inhibition of MAO can be implicated to the cure of such diseases. Synthetic MAO inhibitors are known to inhibit MAO activity. However, there are safety issues with synthetic MAO inhibitors and many of their effects are non-selective and irreversible. Contrasting synthetic drugs, plant-derived natural products have been popularized globally owing to their extensive acceptability and applicability, therapeutic potency and minimum side effects which potentiated the possibility of developing reversible, promising MAO inhibitors based on natural products. The present review comprehensively elucidates plant -derived natural reversible MAO inhibitors using the literature from the popular databases such as Google Scholar, Scopus, PubMed and Web of Science. This literature review reports approximately 51 plants that have been evaluated for MAO inhibitory activity. In addition, 93 plant-derived natural compounds were retrieved as MAO inhibitors. Majority of these investigations predominantly utilized an in vitro approach to evaluate the MAO inhibitors in relation to the developing treatments of related neurological diseases. However, in vivo studies and clinical trials are still lacking in evaluating the botanical-based MAO inhibitors. The aim of this review is to retrieve the recent literature to explore the in vitro and in vivo studies of plant-based natural products as MAO inhibitors, their structure-activity relationship and relevant molecular docking analyses and their roles in the emerging therapy against disorders like AD, and PD. Further, the review also discusses the shortcomings in the existing research in order to generate more coordinated and focused research in future.

Cannabis sativa, widely known as ‘Marijuana’ poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis for both medicinal and recreational purposes suggests it to be a friendly plant. However, whether the misuse of Cannabis and the cannabinoids derived from it can hamper normal body physiology is a focus of ongoing research. On the one hand, there is enough evidence to suggest that misuse of marijuana can cause deleterious effects on various organs like the lungs, immune system, cardiovascular system, etc. and also influence fertility and cause teratogenic effects. However, on the other hand, marijuana has been found to offer a magical cure for anorexia, chronic pain, muscle spasticity, nausea, and disturbed sleep. Indeed, most recently, the United Nations has given its verdict in favour of Cannabis declaring it as a non-dangerous narcotic. This review provides insights into the various health effects of Cannabis and its specialized metabolites and indicates how wise steps can be taken to promote good use and prevent misuse of the metabolites derived from this plant.

The SARS-CoV-2 infection spread rapidly throughout the world and appears to involve in both humoral and cell-mediated immunity. SARS-CoV-2 is attached to host cells via binding to the viral spike (S) proteins and its cellular receptors angiotensin-converting enzyme 2 (ACE2). Consequently, the S protein is primed with serine proteases TMPRSS2 and TMPRSS4, which facilitate the fusion of viral and cellular membranes result in the entry of viral RNA into the host cell. Vaccines are urgently required to combat the coronavirus disease 2019 (COVID-19) outbreak and aid in the recovery to pre-pandemic levels of normality. The long-term protective immunity is provided by the vaccine antigen (or pathogen)-specific immune effectors and the activation of immune memory cells that can be efficiently and rapidly reactivated upon pathogen exposure. Research efforts aimed towards the design and development of vaccines for SARS-CoV-2 are increasing. Numerous coronavirus disease 2019 (COVID-19) vaccines have passed late-stage clinical investigations with promising outcomes. This review focuses on the present state and future prospects of COVID-19 vaccines research and development, with a particular emphasis on immunological mechanisms of various COVID-19vaccines such as adenoviral vector-based vaccines, mRNA vaccines, and DNA vaccines that elicits immunological responses against SARS-CoV-2 infections in humans.

Plumbago zeylanica L. (Plumbaginaceae) is a very important medicinal plant containing plumbagin as the major secondary metabolite synthesized and stored in its roots. Over-exploitation to meet the growing demand on global level has put it under the endangered plant category. The objective of the present study is to provide the desired plant material for industrial use. Adventitious root culture is considered as an alternative source of plant material. In the present study, the leaf explants were inoculated on half-strength Murashige and Skoog (MS) medium supplemented with different plant growth regulators to obtain the adventitious roots in vitro. The leaf explants inoculated on half-strength MS medium supplemented with 6.0 µM 6-benzylaminopurine (BAP) and 2.5 µM 1-naphthaleneacetic acid (NAA) produced maximum roots within the shortest period of time. The current study aims at the optimization of in vitro adventitious roots initiation and growth of P. zeylanica from the leaf explants. The protocol established here can be used for bulk production of P. zeylanica roots for medicinal use.

Alzheimer's disease (AD) is a paramount chronic neurodegenerative condition that has been affecting elderly people since the 1900s. It causes memory loss, disorientation, and poor mental function. AD is considered to be one of the most serious problems that dementia sufferers face. Despite extensive investigation, the pathological origin of Alzheimer's disease remains a mystery. The amyloid cascade theory and the vascular hypothesis, which stresses the buildup of Aβ plaques, have dominated research into dementia and aging throughout history. However, research into this task failed to yield the long-awaited therapeutic miracle lead for Alzheimer's disease. Perhaps a hypothetical fragility in the context of Alzheimer's disease was regarded as a state distinct from aging in general, as suggested by the angiogenesis hypothesis, which suggests that old age is one state associated with upregulation of angiogenic growth factors, resulting in decreased microcirculation throughout the body. There has also been evidence that by controlling or inhibiting the components involved in the sequence of events that cause angiogenesis, there is a visible progression in AD patients. In Alzheimer's disease, one such antiangiogenic drug is being used.

Highlights • Long non coding RNAs (lncRNAs) are non-protein or low-protein coding transcripts. • LncRNAs contain more than 200 nucleotides. • LncRNAs are associated with disease pathogenicity including the neurological disorders. • LncRNAs mediate pathogenesis by decoy, scaffold, mi-RNA sequestrator, histone modifiers and in transcriptional interference. • LncRNAs can serve as novel biomarkers for therapeutic aspects., Long non coding RNAs (lncRNAs) are non-protein or low-protein coding transcripts that contain more than 200 nucleotides. They representing a large share of the cell's transcriptional output, demonstrate functional attributes viz. tissue-specific expression, determination of cell fate, controlled expression, RNA processing and editing, dosage compensation, genomic imprinting, conserved evolutionary traits etc. These long non coding variants are well associated with pathogenicity of various diseases including the neurological disorders like Alzheimer's disease, schizophrenia, Huntington's disease, Parkinson's disease etc. Neurological disorders are widespread and there knowing the underlying mechanisms become crucial. The lncRNAs take part in the pathogenesis by a plethora of mechanisms like decoy, scaffold, mi-RNA sequestrator, histone modifiers and in transcriptional interference. Detailed knowledge of the role of lncRNAs can help to use them further as novel biomarkers for therapeutic aspects. Here, in this review we discuss regulation and functional roles of lncRNAs in eight neurological diseases and psychiatric disorders, and the mechanisms by which they act. With these, we try to establish their roles as potential markers and viable diagnostic tools in these disorders., Graphical abstract Image, graphical abstract

The well-known medicinal plant Centella asiatica (L.) Urban is an Ayurvedic and traditional Chinese medicine used in the treatment of different health problems and as an edible vegetable in a regular diet. Ease of availability in the wide range of environmental conditions plus low-cost cultivation process has made the plant popular in ethno-medicinal healthcare systems. In the present review, phytochemical analysis of plant-extract and pharmacological activities of bioactive-compounds are discussed based upon the available reports to understand their therapeutic potentialities along with the mechanisms behind. The results exhibited that C. asiatica and its triterpenoids demonstrated an array of pharmacological effects and health benefits, some of which were confirmed in many preclinical and clinical studies. Those reports also provided considerable evidences in support of the principles of folk treatment in different countries. Increase and maintenance of the prospective plant secondary metabolites would provide an enriched resource of drug molecules. Development of suitable derivatives of the therapeutic compounds can give an assurance for getting more effective drug candidates with reduced side effects. The review also enumerates the application of advanced nanotechnology, toxicology, and clinical-trial reports on the plant with notes on the shortcomings in the present research and future perspectives of using this medicinal plant.

The COVID-19 pandemic, caused by SARS-CoV-2, is a deadly disease affecting millions due to the non-availability of drugs and vaccines. The majority of COVID-19 drugs have been repurposed based on antiviral, immunomodulatory, and antibiotic potential. The pathogenesis and advanced complications with infection involve the immune-inflammatory cascade. Therefore, a therapeutic strategy could reduce infectivity, inflammation, and immune modulation. In recent years, modulating the endocannabinoid system, particularly activation of the cannabinoid type 2 (CB2) receptor is a promising therapeutic target for modulation of immune-inflammatory responses. JWH133, a selective, full functional agonist of the CB2 receptor, has been extensively studied for its potent anti-inflammatory, antiviral, and immunomodulatory properties. JWH133 modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. In this study, we propose that JWH133 could be a promising candidate for targeting infection, immunity, and inflammation in COVID-19, due to its pharmacological and molecular mechanisms in numerous preclinical efficacy and safety studies, along with its immunomodulatory, anti-inflammatory, organoprotective, and antiviral properties. Thus, JWH133 should be investigated in preclinical and clinical studies for its potential as an agent or adjuvant with other agents for its effect on viremia, infectivity, immune modulation, resolution of inflammation, reduction in severity, and progression of complications in COVID-19. JWH133 is devoid of psychotropic effects due to CB2 receptor selectivity, has negligible toxicity, good bioavailability and druggable properties, including pharmacokinetic and physicochemical effects. We believe that JWH133 could be a promising drug and may inspire further studies for an evidence-based approach against COVID-19.

Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. ‘Memory’ can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain’s hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.

Swertia chirata Buch.-Ham. ex C.B. Clarke is an important medicinal plant used in various herbal formulations as it shows significant biological activities such as hepatoprotective, hypoglycemic, anti-inflammatory, antimalarial, antioxidant and anti-parkinson. C-glucosyl xanthone glycoside (mangiferin) is known as bio-marker compound of genus Swertia L. Development of efficient extraction methods of C-glucosyl xanthone mangiferin from Swertia chirata was attempted by optimizing the pre-harvest, post-harvest and extraction techniques by full factorial design. Firstly, a full factorial design was implemented to evaluate the single and interactive effects of pre-harvest (growth stage and plant part), post-harvest (drying condition and storage periods) followed by selection of best extraction technique such as heat reflux extraction (HRE), microwave assisted extraction (MAE) and ultrasound assistant extraction (UAE) at different solvent types on mangiferin yield. HPTLC and HPLC techniques were used for the determination of mangiferin content in extracts generated from different plant samples. In addition, anti-oxidant and anti-diabetic properties were determined by using DPPH assay and percentage inhibition of α‑amylase enzyme. Substantial variation of mangiferin yield, ranged from 1.46 to 4.86% was observed, depending on the growth stage, plant part, drying condition, storage periods and extraction method. Results showed that drying of the leaves of Swertia chirata in the shade harvested at budding stage and stored for not more than 1 month was recommended for obtaining a higher mangiferin yield. Among different extraction techniques, MAE and UAE in 50% aqueous ethanol solvent were found to be efficient and cost-effective with better yield of mangiferin (4.82% and 4.86%, respectively) as compared to HRE (4.14%). Highest DPPH activity and percentage inhibition of α‑amylase was observed in the aqueous ethanol extract of S. chirata leaves harvested at bud-stage of plant followed by flowering stage. The study shows that optimization of various factors by full factorial design was found to be an effective procedure to improve mangiferin yield from Swertia chirata and can be used for extraction of mangiferin.

Dioscorea deltoidea (Dioscoreaceae) is an endangered species having tubers that possess anextensive range of therapeutic and economic value due to presence of bioactive compound diosgenin. Several industries have various necessities for compounds of specific classes and therefore, choosy extraction strategies for segregation of these classes ought to be produced.The current study aimed to screen potent part, identify best drying process, efficient extraction methods with solvent selection and seasonal variations on diosgenin content in D. deltoidea. The tuber contained the highest diosgenin content (1.15% DW) compared to leaf and stem. The highest yield of diosgenin was obtained using microwave-assisted extraction (MAE) with 50% ethanol (0.99% DW) and minimum incold maceration with water (0.46% DW). Shade drying was found to be the best drying method as compared to others in terms of diosgenin yield (1.43% DW) whereas sun drying produced low yield (1.12% DW). Estimation of yield and enriched diosgenin (1.19% DW) specified that winter (December) is the perfect time to harvest D. deltoidea.

This study was conducted to evaluate the phenolic content, antioxidant potential, and enzyme inhibitiory properties of Rumex nepalensis by in vitro spectrophotometric methods. The experiments demonstrated that glutathione S-transferase (GST), α-glycosidase (α-Gly), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes were strongly inhibited by R. nepalensis extracts. The IC50 values for GST, α-Gly, AChE, and BChE enzyme inhibitions were calculated as 21.01 mg/mL, 34.65 mg/mL, 27.72 mg/mL, and 17.32 mg/mL, respectively. Also, effective antioxidant capacities of water and methanol extracts of R. nepalensis were determined by ABTS, CUPRAC, DPPH, and FRAP methods. Furthermore, quinic acid (15.61 mg/g), miquelianin (2.06 mg/g), quercitrin (1.97 mg/g), and protocatechuic acid (0.217 mg/g) were identified to be the major phenolic compounds of the plant extract according to the LC-MS/MS analysis. Finally, molecular docking studies were carried out to show the interactions of quinic acid, miquelianin, and quercitrin with AChE, BChE, GST, and α-Gly enzymes. Docking analysis indicated the possible roles of these phytochemicals in enzyme inhibitory activities.

Diosgenin is a plant-derived secondary metabolite mainly present in the members of the plant family Dioscoreaceae. It is a pharmaceutically important compound because of its anti-cancerous, anti-diabetic, anticoagulant, anti-thrombosis, anti-inflammatory, anti-viral, anti-ageing and other properties. Biotechnology provides an opportunity to genetically manipulate cells, tissues, organs or the whole organisms by propagating them in vitro in order to harvest the bioactive compounds. Diosgenin production from botanical sources is being improved by in vitro techniques which include elicitation, genetic transformations and bioconversions. Various techniques have been developed to obtain compounds for drug detection including separation from plants and other natural sources, molecular modelling, synthetic chemistry and combinatorial chemistry. Development in molecular markers determines genetic relationship, genetic linkage map construction, genetic diversity and identification. For rapid clonal propagation and ex situ conservation, the in vitro tools involving plant cell, tissue and organ culture have been well documented for plant-derived diosgenin production. The present review encompasses the wide application of the biotechnological techniques for diosgenin production via elucidating its biosynthetic pathway, in vitro production and mass propagation and elicitation. In addition, molecular marker-mediated diversity assessment of diosgenin containing plant species is also discussed. The review also presents the recent literature to explore the limitations of the relevant studies and future direction of research on production of diosgenin from Dioscorea spp. KEY POINTS: • Critical and updated assessment on sustainable production of diosgenin from Dioscorea spp. • In vitro propagation of Dioscorea spp. and elicitation of diosgenin production. • Diversity assessment of Dioscorea spp. using molecular markers.

Medicinally important steroid-based compound diosgenin is usually obtained from the secondary metabolic products of several plant species. Diosgenin has been proven as a prospective bioactive drug lead to the pharmaceutical industries as having anti-cancer activity, anti-microbial activity, anti-thrombic activity, anti-diabetic activity, cardioprotective activity, anti-inflammatory activity, osteoarthritis protective activity etc. Observing the multiple therapeutic values of this compound, scientists and chemists have become interested to discover alternative sources. Endophytic microorganisms possess the potentials producing prospective secondary metabolites. Some diosgenin producing endophytic fungi and bacteria are detected and reported by authors. Extraction and quantification of the respective secondary metabolite in a proper way is required initially for its large scale production. Regular involvement of advance biotechnological approaches plus industrial fermentation technology along with proper funding following government policy is necessary for further progress in this field. Exploration of a higher number of diosgenin producing endophytic strains will definitely increase the supply for social requisition in a cost-effective and environment-friendly manner as limiting the excessive exploitation of plant sources.

The horrifying impact of emergence of cancer as an endemic disease worldwide associated with accelerated mortality rate caused significant boost in anticancer drug discovery. The most successful broad spectrum anti-neoplastic monoterpene indole alkaloid camptothecin (CPT) is the product of such natural product based therapeutic approach. This promising anticancer compound, currently approved against cancer, was first isolated from Camptotheca acuminata of Nyssaceae family and was reported as a potent inhibitor of eukaryotic topoisomerase I. Despite its continuous success under clinical studies, low accumulation, slow growth and over-exploitation of Camptotheca acuminata, high extraction cost, complex nature of total, semi and chemical synthesis has failed to meet the industrial demand. As an alternative bio-prospecting route, fermentation of endophytic microbial culture and co-culture of CPT producing plant cell suspension with endophytes have evolved. Endophytes are reported for their contribution in plant growth, disease resistance, stress tolerance and agricultural productivity which may have contributed to scale up the CPT production. This review sums up the current trend in endophytic microbes-based CPT biosynthesis and biotechnological strategies for optimization of CPT yield. Moreover, interaction of endophytic fungi with different host plants under experimental variables, their mode of elicitation, possibility of microbial strain improvement via application of biotechnological strategies and respective lacunas are also being elucidated.

Cancer is the uncontrolled growth and development of cells in the body, and is one of the foremost reasons of deaths throughout the world. There are over 100 different types of cancers that are categorized on the basis of the affected tissue or organ of the human body. Cancer, a multifactorial malady involves multifarious changes in the genome due to interactions with the individual’s environment. The hallmarks of the cancer are uninhibited replication, inability to respond to growth signals, resulting in arrest of the cell division, continuous angiogenesis, resistance to apoptosis, and the ability to infiltrate other tissues. Currently, cancers can be cured by means of both conventional tonic approaches, i.e., surgery, radiation therapy and chemotherapy, and nonconventional or complementary therapeutic methods, including hormone therapy, immunotherapy, nanotherapy, etc. These well-established therapeutic interventions specifically target the tumors and either inhibit or slow down the growth rate of cells, but incompetent to completely provide protection. Nevertheless, these existing cancer cure practices cause adverse side effects, and largely distress the normal cells, tissues, and organs. Selecting the best cancer therapy approach depends on various factors, such as the type of malignancies, growth stages, age, management frequencies, dosage of medicines, and healthiness of patients. More recently, various molecular-based approaches are being increasingly researched, including gene therapy, targeted silencing by siRNAs, the expression of genes triggering apoptosis and wild tumor suppressors. This chapter discusses about the cancer biology and various conventional and modern treatment approaches to combat diverse forms of cancer.

Neoechinulins are fungal and plant-derived chemicals extracted from Microsporum sp., Eurotium rubrum, Aspergillus sp., etc. Two analogues of neoechinulin, i.e., A and B, exerted extensive pharmacological properties described in this review. Neoechinulin is an indole alkaloid and has a double bond between C8/C9, which tends to contribute to its cytoprotective nature. Neoechinulin A exhibits protection to PC12 cells against nitrosative stress via increasing NAD(P)H reserve capacity and decreasing cellular GSH levels. It also confers protection via rescuing PC12 cells from rotenone-induced stress by lowering LDH leakage. This compound has great positive potential against neurodegenerative diseases by inhibiting SIN-1 induced cell death in neuronal cells. Together with these, neoechinulin A tends to inhibit Aβ42-induced microglial activation and confers protection against neuroinflammation. Alongside, it also inhibits cervical cancer cells by caspase-dependent apoptosis and via upregulation of apoptosis inducing genes like Bax, it suppresses LPS-induced inflammation in RAW264.7 macrophages and acts as an antidepressant. Whereas, another analogue, Neoechinulin B tends to interfere with the cellular mechanism thereby, inhibiting the entry of influenza A virus and it targets Liver X receptor (LXR) and decreases the infection rate of Hepatitis C. The present review describes the pharmaceutical properties of neoechinulins with notes on their molecular, cellular, and functional basis and their therapeutic properties.

The rate of breast cancer has been rapidly increasing over the last few years. Extensive development of breast cancer treatment directed to the discovery of new anticancer drugs. These chemotherapeutic drugs are involved in the suppression of breast cancer, however, toxicity related to these drugs could not be ignored. Paclitaxel is considered as an important drug for breast cancer treatment. Paclitaxel has been utilized for breast cancer treatment as a single agent in first-line therapy, or in combination therapy with other drugs or agents or anti-HER2 antibody. Adjuvant and neoadjuvant clinical trials also displayed paclitaxel efficiency in different types of breast cancer. Apart from paclitaxel efficacy, as demonstrated in this chapter, paclitaxel treatment is also associated with toxicity and chemoresistance. Also, this chapter reviews the role of paclitaxel in the treatment of different types of breast cancer based on clinical trial studies and paclitaxel related toxicities and chemoresistance.

Hemidesmus indicus (L.) R. Br. ex Schult., commonly known as Indian sarsaparilla or Anantamul, is an ethnopharmacologically important medicinal plant from the family Apocynaceae. Biosynthesis of an array of bioactive compounds such as methoxybenzaldehydes and their derivatives has been accountable for its intensive medicinal attributes. Low seed setting, over-exploitation from natural habitat and a need for selection and preservation of elite germplasms yielding higher levels of bioactive compounds have led researchers to enquire the standardization of micropropagation techniques and quantitative estimation of phytochemicals from H. indicus. The present work aims to have a comprehensive account on micropropagation in H. indicus, a comparative estimation of biotic and abiotic factors, viz. elicitors and precursors playing a crucial role in H. indicus tissue culture, a critical appraisal of applied protocols to nullify embellished claims and a discussion on future perspectives. The review also highlights the comparative effect of different plant growth regulators as well as their combined role in rhizogenesis, callogenesis, base callus formation, callusing and somatic embryo-mediated indirect organogenesis, outcome of explant selection, contribution of abiotic (temperature, photoperiod, moisture, inorganic molecules) factors, role of carbon source, application of sterilization techniques and associated success rates, role of factors essential for acclimatization and secondary metabolite production, synthetic seed production and genetic transformation techniques. The compiled information along with individual study details, respective outcome and variability of reports will aid in proper assessment of cited standardized tissue culture protocols in H. indicus especially in relation to secondary metabolite production. Moreover, the assessment of applicability of different methodologies in this aspect will aid in the selection of high-yielding germplasms or chemotypes which is not only profitable for industrial application but also important for basic and applied preclinical and clinical research studies. KEY POINTS: • Critical and updated assessment on in vitro biotechnology in Hemidesmus indicus. • Biotechnological advancement via Agrobacterium-mediated transformation. • Key shortcomings and future research directions Graphical abstract Effect of biotic and abiotic factors on Micropropagation and secondary metabolite synthesis in Hemidesmus indicus.

Background The amphibian, non-vascular, gametophyte-dominant, bio-indicator class, bryophytes; with their wide ranges of habitat have attained importance due to their promising medicinal attributions and therapeutic role; mostly aided by presence of aromatic bibenzyl and bisbybenzyl class of compounds. Bibenzyls are steroidal ethane derivatives, resembling the structural moiety of bioactive dihydro-stilbenoids or iso-quinoline alkaloids. These stress triggered secondary metabolites are the by-products of the flavonoid biosynthetic pathway. Different classes of bryophytes (Bryophyta, Marchantiophyta and Anthocerotophyta) possess different subtypes of bibenzyls and dimeric bisbibenzyls. Among the liverwort, hornwort and mosses, former one is mostly enriched with bibenzyl type constituents as per the extensive study conducted for phytochemical deposit. Considering macrocyclic and acyclic group of bibenzyls and bisbybenzyls, generally marchantin type compounds are reported vividly for significant biological activity that includes neuro-nephro-cardio-protection besides anti-allergic, anti-microbial, anti-apoptotic and cytotoxic activities studied on in-vitro and in-vivo models or on cell lines. Result The critical analysis of reported chemical and pharmaceutical attributions of bibenzyls and bis-bibenzyls yielded detailed report on this compound class along with their application, mode of action, natural source, techniques of synthesis, extraction procedure, isolation and characterization. Further, the structure activity relationship studies and bioactivity of bibenzyls derived from non-bryophytic origin were also summarized. Conclusion This review encompasses prospective biological application of botanical reservoir of this primarily ignored, primeval land plant group where recent technical advances has paved the way for qualitative and quantitative isolation and estimation of novel compounds as well as marker components to study their impact on environment, as bio-control agents and as key leads in future drug designing. Graphical abstract

Purulia, the land of distinctive geological and archaeological features, abundant natural resources and a home to a number of aboriginals, has been studied widely to apprehend the role of ethnic remedies against myriad of diseases. Availability of natural remedies and practice of traditional knowledge have popularized the use of medicinal plants among local communities. The objective of the study is to elucidate the use of folk medicine against common otorhinolaryngologic and ophthalmic medical conditions, by various ethnic groups of Purulia district, West Bengal, India. A completely randomized ethnobotanical approach was carried out during a number of field visits conducted to interview 55 traditional healers (THs) residing across the 20 blocks of district Purulia via semi-structured open-ended questionnaire. The similarity of usage of plants for different diseases was calculated by the informant consensus factor (Fic), whereas fidelity level indicated the plants mostly cited by the informants. The correlative importance of the usage of the plants was measured by the use value (UV). A total number of 28 plant species belonging to 27 genera and 20 families are reported in this present study in the treatment of a number of otorhinolaryngologic and ophthalmic ailments such as cough and cold, eye diseases (sore eye, red eye, eye inflammation and conjunctivitis), ear diseases (earache and pus in ears), nosebleed and throat infection. The highest value for informant’s consensus factor (Fic) was observed in cough and cold (0.87) that indicates most of the plants possess analgesic and antipyretic potential, whereas the lowest value (0.33) was shown by sore eye that denotes least number of plants have been applied for eye cure. Mostly, leaf part (41.4%) is utilized to cure selected otorhinolaryngologic and ophthalmic disorders where most of the herbal formulations were applied as leaf juices (60.7%). Most significant plant species were Piper nigrum L., Ocimum sanctum L. and Zingiber officinale Roscoe according to their highest UV (1.80), followed by Andrographis paniculata (Burm. f.) Wall. ex Nees (1.79) and Justicia adhatoda L. (1.66). The present work represents first quantitative ethnobotanical study against some tropical otorhinolaryngologic and ophthalmic disorders in remote areas of Purulia district where acute poverty, underprivileged livelihood, illiteracy, unavailability of conventional health care as well as age-old trust on THs have popularized the use of natural resources (i.e. medicinal plants). Many of the reported ethnomedicinal properties of some plants have been backed up by clinical data also. Aboriginal people also showed keen interest and knowledge regarding conservation of endangered medicinal plants and on sustainable utilization of botanical resources. Proper documentation of traditional knowledge and potential preclinical and clinical studies based on the ethnobotanical data procured may be suggested for safe and efficacious use of herbal medicine against otorhinolaryngologic and ophthalmic disorders.

Several plant-derived neuroprotective nutraceuticals have shown their neuroprotective efficacy in various in vitro, in vivo, and clinical investigations. These molecules represent diverse types of chemical structures such as organosulfur, flavone, flavonol, alkaloid, polyphenol, and isothiocyanate. Neuroprotection offered by these molecules is mediated by antioxidation, anti-apoptosis, and anti-inflammation and by maintaining mitochondrial functionality. These nutraceuticals also prevent neurodegeneration by modulating several signaling pathways and gene expression. These include regulation of NOS via Akt and ERK, enhancement of mitochondrial function, downregulation of MAPK pathways, reducing convulsions, upregulating amyloidogenic route of brain APP processing, upregulating Keap1/Nrf2 pathway, and modulating NF-κB activation via the p38MAPK/PKC pathway and so on. Due to their ability to target multiple factors responsible for neuronal loss, they can serve as an excellent therapeutic agent to combat the complex nature of most of these neurodegenerative diseases. The present review focuses on the role of such botanical-derived nutraceuticals in the protection and prevention of several neurodegenerative diseases in vitro and in vivo mediated by their ability to modulate several signaling pathways, molecules, and gene expression to control various pathophysiological features of such diseases.

The environmental consciousness and consumer pressure have forced manufacturing industries to use natural fibres as a substitute for conventional non-renewable reinforcing materials. In the present investigation, the effect of rate of loading on jute fibre-reinforced polymer composite was studied. The mechanical properties (in three-point bend test) like interlaminar shear strength, yield strength and energy at break were examined as a function of strain rate. It was observed that the untreated fibre-reinforced composites were not very sensitive to the rate of loading; however, loading rate sensitivity was observed in alkali-treated fibre-reinforced composites. It has been proposed that fibre pull-out dominates over mechanism of composite failure in alkali-treated condition, and the interlaminar shear strength/yield strength was increased due to the increase in stiffness of the composite with rate of loading (in initial stage); however, at higher strain rate, matrix became susceptible to brittleness as there was lesser time available for crack-blunting to take place. All the microstructures were generated using a scanning electron microscope, and mechanical testing was done using tensile testing machine Instron 1195.

Frequent use of medicinal plants is common in healthcare needs of mankind since ancient ages. Among these Moringa oleifera Lam. is one of the vastly used plant whose various parts (leaf, fruit, seeds etc.) are included in regular diet for their multiple ability of combating several health issues. WHO has highlighted on the proper utilization of natural products and marked plant-based medicines as prime study candidates. Taking initiative to explore bioactive leads other than conventional chemotherapeutic agents (with undesirable side effects) have drawn attention of the scientists involved in viral research due to the lack of effective vaccines and insufficient supply of existing costly drugs to socio-economic demands. Several studies were reported regarding the antiviral activity of M. oleifera plant, a pronounced bioprospective aspirant. The plant is known to be used in many traditional medicines and pharmacopeias against an array of medical conditions that include malaria, diabetes, skin infection, tuberculosis, anemia, headaches, epilepsy, sexually transmitted diseases and so on. In African traditional medicine, the plant is popularly used against AIDS and related secondary infections associated with HIV. It showed significant activities against viruses like HIV, HSV, HBV, EBV, FMDV and NDV. In some cases active molecules with mode of actions were documented by authors. On the other hand, there is a number of reports where neither lead compounds nor the relevant mechanisms were clarified regarding the viral inhibitory activities of crude plant extract. Immense studies should be going on to resolve those unanswered motifs along with the well planned trials of clinical application of already discovered potent phytochemicals. For conducting the continuous investigational groundwork in this field, the respective plant should be preserved with proper maintenance, necessarily.

Funding Information: The authors sincerely acknowledge the research fund support from ADEK award for Research Excellence (AARE18-194). The authors also acknowledge the research grant (21R075) from Zayed Bin Sultan Al Nahyan Center for Health Sciences (ZCHS), UAE University, UAE. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

Cancer is probably the deadliest human disease in recent years. In the past few years, rapid clinical progress has been made in the field of anticancer drug development. Plant secondary metabolites have been noted as extremely efficacious as promising natural source for anticancer therapy for many years. Camptothecin (CPT) is one of the popularly used anti-tumor drugs possessing clinically proven properties against a plethora of human malignancies that include ovarian and colorectal cancers. For the first time, CPT was obtained from the extracts of a Chinese medicinal tree, Camptotheca acuminata Decne. from the family Cornaceae. Subsequently, CPT was also isolated from the bark of Nothapodytes foetida (Wight) Sleumer (Icacinaceae). However, the availability of enough natural sources for obtaining CPT is a major constraint. Due to overexploitation and harvesting, loss of habitat, excessive trading, and unfavorable environmental factors, the natural source of CPT has become extinct or extremely limited and hence they are red listed under endangered species. Conventional propagation has also failed to meet the ever-expanding demand for CPT production. With this, biotechnological toolkits have constantly been used as a boon to produce sustainable source, utilization, and ex situ conservation of medicinal plants. The approaches serve as a supplement to traditional agriculture in the mass production of plant metabolites with potent bioactivities. Non-availability of enough anticancer medicine and the requirement to satisfy current demands need a sustainable source of CPT. With this background, we present a comprehensive review on CPT discovery, its occurrence in the plant kingdom, biosynthesis, phytochemistry, pharmacological properties, clinical studies, patterns of CPT accumulation, and biotechnological aspects of CPT production in three plants, viz., N. nimmoniana, Ophiorrhiza species, and C. acuminata.Key points• Biotechnological approaches on production of camptothecin from Nothapodytes nimmoniana, Ophiorrhiza species, and Camptotheca acuminata• In vitro propagation of camptothecin-producing plants• Genetic diversity and transgenic research on camptothecin-producing plants.

Antibiotic resistance or microbial drug resistance is emerging as a serious threat to human healthcare globally, and the multidrug-resistant (MDR) strains are imposing major hurdles to the progression of drug discovery programs. Newer antibiotic-resistance mechanisms in microbes contribute to the inefficacy of the existing drugs along with the prolonged illness and escalating expenditures. The injudicious usage of the conventional and commonly available antibiotics in human health, hygiene, veterinary and agricultural practices is proving to be a major driver for evolution, persistence and spread of antibiotic-resistance at a frightening rate. The drying pipeline of new and potent antibiotics is adding to the severity. Therefore, novel and effective new drugs and innovative therapies to treat MDR infections are urgently needed. Apart from the different natural and synthetic drugs being tested, plant secondary metabolites or phytochemicals are proving efficient in combating the drug-resistant strains. Various phytochemicals from classes including alkaloids, phenols, coumarins, terpenes have been successfully demonstrated their inhibitory potential against the drug-resistant pathogens. Several phytochemicals have proved effective against the molecular determinants responsible for attaining the drug resistance in pathogens like membrane proteins, biofilms, efflux pumps and bacterial cell communications. However, translational success rate needs to be improved, but the trends are encouraging. This review highlights current knowledge and developments associated challenges and future prospects for the successful application of phytochemicals in combating antibiotic resistance and the resistant microbial pathogens.

With more than 100 million cases and over 2 million deaths globally, the COVID-19 pandemic continues to remain a major threat. Identifying the behavioral factors influencing preventive behaviors for COVID-19 are crucial in devising public health policies to promote essential strategies to combat the pandemic in an efficient manner. The current study was therefore conducted to estimate the prevalence of COVID-19 preventive behaviors and measure their association with behavioral constructs like threat perception, response efficacy, and self-efficacy, as per socio-demographic background. A region-stratified online survey focusing on the constructs of protection motivation theory, for example, threat and coping appraisal for preventive health practices against COVID-19, was carried out among adult users of social media in India. Generalized linear models with cluster-adjusted-robust standard errors were used to analyze the responses and model the preventive practices among the study population. Analysis of a total 2,646 responses revealed that proper perceptions regarding cause, symptoms, and transmission of COVID-19 were prevalent in the majority of the respondents. The majority of the participants reported frequent use of face masks (93.20%), followed by frequent washing of hands with soap and water (84.90%). The majority of the respondents affirmed that, though not frequently but sometimes, they avoid touching the face with unclean hands. Frequently covering mouth with the crook of the elbow while sneezing and coughing, and maintaining physical distance when outside was noted among 74.14 and 83.84%, respectively. The proportion of participants frequently using sanitizers to clean hands and those infrequently practicing the same were comparable. Self-efficacy for preventive practices and threat-appraisal of COVID-19 illness were identified as important determinants of the selected COVID-19 preventive behaviors, independently. The analysis confirmed that practices of the behaviors were mostly synergistic to each other. Current findings highlight that formulation of precise risk communication strategies to improve perceptions regarding threat appraisal and self-efficacy could facilitate desirable practices, which are also effective in the prevention of airborne infections and, hence, may contribute toward broader policy directions. The evidence urges the implementation of precision-driven risk communication and diffusion of these practices to attain behavioral herd immunity.

Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.

Introduction: Due to COVID-19 pandemic, performance of many program has been declined and Tuberculosis (TB) program is not an exception. TB case detection and notification has been recognized as one of worst hit area. The objective of this study was to explore the TB notification status of India during this pandemic and explore options to mitigate the issue. Methods: A secondary data analysis was performed on open source TB notification database of India. Relevant literature review was done to find out remedies based on the different initiative taken by different states of India. Results: In 2020, total TB notification decreased in all the states in comparison to 2019. The percentage of loss in the country was 34%. Private TB notification also decreased in 2020 in all the states except in Jharkhand. The percentage of loss in private TB notification in the country was 35%. Notification started declining in the month of February 2020 and it was lowest in the month of April-2020. The trend of notification began to improve since May 2020 when the States started taking innovative initiatives like Integrated TB Covid Case Search. Conclusion: Due to the ongoing COVID-19 pandemic the notifications of TB cases declined noticeably which has a serious implication in terms of silent spread within household and community. But the picture can be improved with integrated approach for TB-COVID case finding and management.

Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.