Chemical composition, antioxidant, antimicrobial, and wound healing effects of Trachyspermum roxburghianum (DC.) H. Wolff essential oil: An in vivo and in silico approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Trachyspermum roxburghianum (DC.) H. Wolff, commonly known as 'Ajamoda,' is a neglected Indian spice highly used in Ayurveda and folklore remedies as an antimicrobial for chronic wounds and discharges, along with many other disease conditions. AIM OF THE STUDY: The objective of the study was to explore chemical composition and to investigate the antioxidant, antimicrobial, analgesic, and wound healing activities of T. roxburghianum fruit essential oil from India. MATERIALS AND METHODS: The phytochemical characterization of the oil was determined through standard qualitative procedures and the gas chromatography-mass spectrometry (GC-MS) technique. The in vitro antioxidant aptitude was assessed by scavenging DPPH and ABTS radicals. The antimicrobial potential of the oil was investigated using the disc diffusion method, followed by the determination of minimum inhibitory concentration against Gram-positive and Gram-negative bacterial and fungal strains. The analgesic potential was evaluated using thermal and chemically induced pain models in Swiss albino mice. Wound healing was assessed in vivo, including determining wound contraction rates, histopathology, and hydroxyproline estimation, using the excision wound model in Swiss albino mice. RESULTS: GC-MS analysis identified 55 compounds with major terpenoids, including thymol (13.8%), limonene (11.5%), and others. Substantial radical-scavenging activity was exhibited by T. roxburghianum fruit essential oil (TREO) (IC50 94.41 ± 2.00 µg/mL in DPPH assay and 91.28 ± 1.94 µg/mL in ABTS assay). Microorganisms were inhibited with low MIC (2 µL/mL for the inhibition of Staphylococcus aureus and Bacillus subtilis; 4 µL/mL against Salmonella typhi and 16 µL/mL against Candida albicans). In the cytotoxicity study, no cytotoxicity was observed on the Monkey Normal Kidney Cell line (Vero). Significant antinociceptive effects were observed (25.47 ± 1.10 % of inhibition at 100 mg/kg and 44.31 ± 1.69 % at 200 mg/kg). A remarkable rate of wound closure and epithelization, along with a marked increase in hydroxyproline content, were observed for the oil during wound healing in mice. CONCLUSIONS: The results suggested that oil could be utilized as a potential source of wound healing therapeutics.

Nutritional Composition, Mineral Profiling, In Vitro Antioxidant, Antibacterial and Enzyme Inhibitory Properties of Selected Indian Guava Cultivars Leaf Extract.

Psidium guajava L. is a small evergreen tree known for its magnificent medicinal and nutritional value. This study aimed to evaluate the nutritional profile and in vitro pharmacological potentialities of the different leaf extracts of four cultivars of Psidium guajava namely Surka chitti, Allahabad safeda, Karela, and Lucknow-49. The standard procedures of the Association of Official Analytical Chemists (AOAC) were followed to carry out the nutritional analysis and all of the cultivars recorded the presence of elements at a nominal range. The highest presence of phenols (125.77 mg GAE/g) and flavonoids (92.38 mg QE/g) in the methanolic leaf extract of the Karela cultivar was recorded. A wide range of minerals such as sodium, phosphorus, magnesium, zinc, and boron were recorded with a higher percentage in the Karela cultivar of Psidium guajava. In the enzyme inhibitory assays, Allahabad safeda showed potential inhibition with an IC50 of 113.31 ± 1.07, 98.2 ± 0.66 and 95.73 ± 0.39 µg/mL in α-amylase, α-glucosidase, and tyrosinase inhibition assays, respectively. The strong antioxidant effect was established by Lucknow-49 (IC50 of 74.43 ± 1.86 µg/mL) and Allahabad safeda (IC50 of 78.93 ± 0.46 µg/mL) for ABTS and DPPH assays, respectively. The ethyl acetate and methanolic leaf extracts of the Allahabad safeda cultivar showed better inhibition against Pseudomonas aeruginosa with an MIC of 14.84 and 28.69 µg/mL, respectively. A decent mean zone of inhibition was recorded in methanolic leaf extract that ranged from 21-25 mm in diameter against the tested bacterial strains (Proteus vulgaris, Bacillus subtilis, and P. aeruginosa). This is the first scientific report on the comparative and comprehensive analysis of indigenous guava cultivars to evidently shortlist the elite cultivars with enriched dietary nutrition and biological activities.

Unravelling the Untapped Pharmacological Potential of Plant Molecules as Inhibitors of BACE1: In Silico Explorations for Alzheimer's Disease.

Alzheimer's disease (AD) is an extremely complex, heterogeneous, and multifactorial neurodegenerative disease clinically characterized by progressive memory loss and progressive decline in cognitive function. There is currently no effective treatment for the onset and/or progression of the pathophysiological diseases of AD. The global prevalence of this disease has increased in recent years due to modern lifestyle. Therefore, there is an urgent need to develop a drug with significant neuroprotective potential. Since plant metabolites, especially polyphenols, have important pharmacological properties acting against ß-amyloid (Aß), Tau, neuroinflammation, and oxidative stress, such phytochemicals were selected in the present research. Using the Schrödinger tool (Maestro V.13.6), the drug potency of these metabolites was studied after installation in the highly configured workstation. Among the 120 polyphenols docked, amygdalin showed notable docking values of - 11.2638, followed by eriocitrin (- 10.9569), keracyanin (- 10.7086), and amaroswerin (- 9.48126). The prominent MM-GBSA values of these molecules were - 62.8829, - 52.1914, - 68.6307, and - 63.1074, respectively. The MM-GBSA energy values demonstrated the drug stability of these molecules for ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1)-causing AD. In the absorption and distribution assessment, these phytochemicals showed significantly better values than the inhibitors CNP520. The chosen phytochemicals have been demonstrated as non-hepatotoxic; however, the BACE1 inhibitor CNP520 is hepatotoxic. In both the molecular docking and ADMET assessments, these natural chemicals have shown optimism as potential drug candidates for Alzheimer's disease. However, in order to understand the detailed biological metabolism of these compounds in AD, they need to be evaluated in in vivo studies to validate its efficacy.

Phytochemical profile, antioxidant, cytotoxic and anti-inflammatory activities of stem bark extract and fractions of Ailanthus excelsa Roxb.: In vitro, in vivo and in silico approaches.

This study aimed to assess the phytochemical composition, in vitro antioxidant, cytotoxicity, and in vivo anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40-22.91 mg/g QE), phenolics (1.72-7.41 mg/g GAE), saponins (33.28-51.87 mg/g DE), and alkaloids (0.21-0.33 mg/g AE). The antioxidant potential was evaluated in vitro using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the in vivo anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the in vitro experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The in-silico results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional in vivo and in vitro studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.

Effect of "Murcchana samskara" on therapeutic efficacy of BhallatakadiGhrita.

'Bhallatakadi Ghrita' (BG), comprising the plant extracts of Semecarpus anacardium L., Argemone mexicana L., Cocculus hirsutus L., and Woodfordia fruticosa K. 'Murcchana samskara' of ghee before any 'ghrita-paka' preparation evidenced the maximum acceptability for topical application. The current study dealt with the effect of the 'Murcchana' process on the therapeutic efficacy of BG. In the first step, 'Murcchita' ghee was prepared as per reference texts and then developed the 'Murcchita Bhallatakadi Ghrita' (M-BG), which was further assessed for wound healing activity using incision and excision wound animal models. 'Murcchanasamskara' altered the wound healing ability of M-BG (100% wound contraction on 15th post wounding day with 13.50 ± 0.22 days complete re-epithelization time and 562.33 ± 7.37 g breaking strength). The presence of antioxidants, polyphenols, flavonoids, and fatty acids (known for their potential wound healing properties) in M-BG could accelerate the wound contraction rate (P < 0.001). The present investigation has corroborated the Ayurvedic/traditional attribute of 'Murcchanasamskara' to augment the medicinal properties of the BG.

Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19.

Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (Mpro/3CLpro) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources.

A review on ethnomedicinally important pteridophytes of India.

ETHNOPHARMACOLOGICAL RELEVANCE: Pteridophytes have been considered an excellent source of medicine since ancient times and remain underexplored in ethnobotanical aspects when compared to other vascular plants. Hence, an attempt has been made to compile medicinally important pteridophytes used by different ethnic minorities and local people in India. MATERIALS AND METHODS: Relevant information on the uses of pteridophytes was extracted from scientific journals (local, regional, and international), books, book chapters, conference proceedings, M.Sc. and Ph.D. dissertations, and other scientific databases. Recent and accepted names of plants were validated using standard nomenclature databases. RESULTS: In total, 283 species of pteridophytes are enumerated in this review which are used to treat 129 ailments. Ethnobotanical records from the states Madhya Pradesh, Tamil Nadu, Assam, Arunachal Pradesh, and Uttarakhand revealed 59% of overall uses of pteridophytes from India. Pteridaceae was recorded with highest number of medicinally important species (57), followed by Polypodiaceae, Dryopteridaceae, Thelypteridaceae, and Aspleniaceae with 36, 27, 22, and 21 species respectively. CONCLUSIONS: The use of medicinal plants in the primary healthcare of humans and livestock has been documented since ancient times, and they offer a useful source of new therapeutics. While pteridophytes have considerable importance in traditional pharmacopoeias, scientific studies on pharmacology of this group are scanty. Hence, studies on the phytochemistry and pharmacology of medicinally important pteridophytes with more citations may reveal active principles that can be further developed into novel therapeutic agents. Records of indigenous medicinal knowledge about pteridophytes need to be given top priority to aid the protection of such knowledge before they vanish from present day traditional healers.

Metabolic variations, antioxidant potential, and antiviral activity of different extracts of Eugenia singampattiana (an endangered medicinal plant used by Kani tribals, Tamil Nadu, India) leaf.

Eugenia singampattiana is an endangered medicinal plant used by the Kani tribals of South India. The plant had been studied for its antioxidant, antitumor, antihyperlipidemic, and antidiabetic activity. But its primary and secondary metabolites profile and its antiviral properties were unknown, and so this study sought to identify this aspect in Eugenia singampattiana plant through different extraction methods along with their activities against porcine reproductive and respiratory syndrome virus (PRRSV). The GC-MS analysis revealed that 11 primary metabolites showed significant variations among the extracts. Except for fructose all other metabolites were high with water extract. Among 12 secondary metabolites showing variations, the levels of 4-hydroxy benzoic acid, caffeic acid, rutin, ferulic acid, coumaric acid, epigallocatechin gallate, quercetin, myricetin, and kaempferol were high with methanol extract. Since the flavonoid content of methanol extracts was high, the antioxidant potential, such as ABTS, and phosphomolybdenum activity increased. The plants antiviral activity against PRRSV was for the first time confirmed and the results revealed that methanol 25 µg and 75 to 100 µg in case of water extracts revealed antiviral activity.