A comprehensive review on Phyto-MAP: A novel approach of drug discovery against Mycobacterium avium subspecies paratuberculosis using AYUSH heritage.

ETHNOPHARMACOLOGICAL RELEVANCE: Indian system of Traditional medicine, AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) has great potential with a History of Safe Use (HOSU) of thousands of medicinal plants included in pharmacopoeias. The multi-targeted approach of phytoconstituents present in different traditionally used medicinal plants makes them suitable candidates for research against various infective pathogens. MAP which is a dairy-borne pathogen is associated with the development of Johne's disease in ruminants and Crohn's disease like autoimmune disorders in human beings. There are no reliable treatment alternatives available against MAP, leaving surgical removal of intestines as the sole option. Hence, there exists an urgent need to search for leads against such infection. AIM OF THE STUDY: The present review has been conducted to find out the ethnopharmacological evidence about the potential of phytoconstituents against Mycobacterium avium subspecies paratuberculosis (MAP), along with the proposal of a potential phyto-MAP mechanism for the very first time taking anti-inflammatory, immunomodulatory, and anti-microbial traditional claims into consideration. MATERIALS AND METHODS: We have analyzed and reviewed different volumes of the two main traditional scriptures of India i.e. Ayurvedic Pharmacopoeia of India (API) and Unani Pharmacopoeia of India (UPI), respectively-for identification of potential anti-MAP plants based on their claims for related disorders. These plants were further investigated systematically for their scientific publications of the last 20 years (2002-2022) available through electronic databases including Google Scholar, Pubmed, and Scopus. The studies conducted in vitro, cell lines, and in vivo levels were taken into consideration along with the associated mechanisms of phytoconstituents. RESULTS: A total of 70 potential medicinal plants have been identified. Based on the ethnopharmacology, a potential phyto-paratuberculosis (Phyto-paraTB) mechanism has been proposed and out of 70, seven potential anti-MAP plants have been identified to have a great future as anti-MAP. CONCLUSION: A novel and scientifically viable plan has been proposed for addressing anti-MAP plants for stimulating research against MAP and related disorders using mass-trusted AYUSH medicine, which can be used as an alternative remedy in resistance cases otherwise can be advocated as an adjuvant with modern treatments for better management of the disease.

Antiviral Potential of Traditional Unani Medicine with Special Emphasis on Dengue: A Review.

Dengue fever has become a major public health concern. It is usually related to intravascular leaking, bleeding disorders, and thrombocytopenia and is recognized as a potent threat to humans. The scarcity of anti-dengue medication or vaccine for such a serious disease leads to an upsurge in the usage of traditional medicines for its proper management. India has diverse biodiversity and a long history of using plant-based remedies. Several medicinal plant extracts have been studied for producing anti-dengue viral activity. AYUSH traditional systems provide a plethora of plants that have been reported to be useful in the treatment of fever. Single and compound plant- based formulations in natural form have been used in Unani holistic approaches. This review serves as a new approach to illustrate the most recent evidence regarding the antiviral activity of various plants by providing scientific proof and also to validate the traditional formulations as effective treatments in dengue fever for global acceptance.

TLC-MS-Bioautographic Identification of Antityrosinase Compounds and Preparation of a Topical Gel Formulation from a Bioactive Fraction of an RSM-Optimized Alcoholic Extract of Rubia Cordifolia L. stem.

BACKGROUND: Rubia cordifolia L., Rubiaceae, is globally reported to treat skin-related problems. The study aimed to assess the antityrosinase potential of Rubia cordifolia (ARC) and the development of gel formulation. METHODS: The AutoDock Vina (version V.1.2.0) program package was used for molecular docking to check for the binding affinity of ligands with protein. Response surface methodology (RSM) software was used to optimize extraction parameters for an alcoholic extract of Rubia cordifolia (ARC). The developed HPTLC method for the quantification of purpurin in ARC was validated as per the International Conference on Harmonization (ICH) guidelines. A bioautographic study for the evaluation of antityrosinase effects was performed; an anthraquinone-enriched fraction (AEF)-loaded gel formulation developed and evaluated physicochemically which could be used to reduce skin pigmentation. RESULTS: Purpurin showed optimum binding affinity (-7.4 kcal/mol) with the molecular target (tyrosinase) when compared to that of standard kojic acid (-5.3 kcal/mol). Quantification of purpurin in ARC, optimized by RSM software, was validated and physiologically significant results were observed for the antityrosinase potential of an AEF, along with TLC-MS-bioautographic identification for antityrosinase compounds: purpurin (m/z 256.21) and ellagic acid (m/z 302.19). Evaluation of an AEF-loaded gel formulation by in vitro and ex vivo permeation studies was performed. CONCLUSION: ARC extraction parameters optimized by RSM, and a bioautographic study helped identify antityrosinase compounds. The development of a gel formulation could be a cost-effective option for the treatment of depigmentation in the future. HIGHLIGHTS: A TLC-MS-Bioautography-based Identification of Antityrosinase Compounds and development of AEF-loaded Topical Gel formulation from a Bioactive Fraction of an RSM-Optimized Alcoholic Extract of Rubia Cordifolia L. stem, which could help with promising results in reducing skin pigmentation and maintaining even tone.

A Comprehensive Study to Explore Tyrosinase Inhibitory Medicinal Plants and Respective Phytochemicals for Hyperpigmentation; Molecular Approach and Future Perspectives.

Tyrosinase is a copper-containing key substance in the pigmentation of mammalian hair and skin. Melanin synthesis is influenced by a variety of extrinsic and internal variables, including hormone fluctuations, inflammation, ageing, and subsequent ultraviolet light exposure. Melasma, senile lentigines, freckles, and diminished colour are all undesirable side effects of excessive melanin production. The current review provides the pursuit of effective and safe tyrosinase inhibitors derived from medicinal plants and ascribes updated inferences on current practices. Commercially available tyrosinase inhibitors provide an even skin tone and are used clinically to treat hyperpigmentation and related disorders. This review focuses on the mechanism of melanogenesis and on experimentally verified potent and natural tyrosinase inhibitors. Bioactive compounds such as phenols, flavonoids, stilbenes, and few traditional herbal formulations from the Indian system of medicine, have been used for long in India and subcontinents for the effective management of melanogenesis and related problems. Scientific information was gathered from different sources of databases such as PubMed, Google Scholar, Springer, Scopus, and Science Direct, as well as the literature found in medicinal plant books. This critically summarized review ensures to aid researchers and enterprises working on tyrosinase inhibitors and on conditions associated with melanogenesis, to get one-step solutions for identifying more safe and effective natural remedies.

A critical review on the extraction and pharmacotherapeutic activity of piperine.

Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice. It is particularly valued for its pungency attributed to its principal constituent - piperine. This review summarizes the information on the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity - analgesic, immunomodulatory, anti-depressive, anti-diarrheal, hepatoprotective, etc. The effect of piperine on biotransformation of co-administered drugs is also presented in this review, along with the mechanisms involved in its bioavailability-enhancing effect. Its important medicinal uses, including anti-hepatotoxic, anti-diarrheal, anti-depressive, analgesic, and immunomodulatory effects, besides many other traditional uses, are compiled. Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of the Piperaceae family.

Development of Synergy-Based Combination for Learning and Memory Using in vitro, in vivo and TLC-MS-Bioautographic Studies.

The present study is aimed at developing a synergistic combination to enhance learning and memory in Alzheimer's patients with the help of eight common medicinal plants used in the AYUSH system. Aqueous and hydroalcoholic extracts of eight medicinal plants from the AYUSH system of medicine were prepared. These were subjected to in vitro anticholinesterase activity, to find out the combination index of synergistic combination. The synergistic combination and their individual extracts were subjected to total phenol, flavonoid and antioxidant activity estimation. Further, in vivo neurobehavioral studies in rats were carried out followed by TLC-MS-bioautographic identification of bioactive metabolites. Out of the sixteen extracts, aqueous extracts of Withania somnifera (L.) Dunal (WSA) and Myristica fragrans (L.) Dunal (MFA) were selected for the development of synergistic combination based on their IC50 value in vitro anticholinesterase assay. The synergistic combination inhibited the anticholinesterase activity significantly as compared to the individual extracts of WSA and MFA. The synergistic combination also showed more phenolic and flavonoid contents with potential antioxidant activity. The TLC-bioautography showed four white spots in WSA, signifying sitoindosides VII, VIII, quercetin, isopelletierine and Withanolide S as AChE inhibitory compounds while showing five white spots of anti-cholinesterase active metabolites identified as eugenol, methyl eugenol, myristic acid, galbacin and ß-sitosterol in MFA. The observation of neurocognitive behavior in amnesia induced subjects manifested that both the synergistic combinations showed comparable results to that of standard piracetam, though the synergistic combination containing a higher concentration of WSA showed more appreciable results in ameliorating dementia in rats. The study suggests that the synergy based combination successfully enhanced memory and learning by abating free radical and acetylcholine levels, and increased learning and memory in rats, providing a strong rationale for its use in the treatment of dementia and Alzheimer's disease.