Chemo-profiling and exploring therapeutic potential of Momordica dioica Roxb. ex Willd. for managing metabolic related disorders: In-vitro studies, and docking based approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica dioica Roxb. ex Willd. (M. dioica Roxb.) a nutritious and therapeutic property rich crop of Cucurbitaceae plant family. In various folklore medicine including Ayurveda fruits are used to treat several metabolic related disorders i.e., hyperglycemia, hyperlipidemia, diabetes, obesity etc. Furthermore, traditionally it is used to treat fever, inflammation, ulcer, skin diseases, haemorrhoids, hypertension and also employed as cardioprotective, hepatoprotective, analgesic, diuretic. AIM OF THE STUDY: This study focuses to explore the therapeutic potential of Momordica dioica Roxb. ex Willd. through in-vitro and in-silico approach for managing hyperlipidemia, hyperglycemia and related metabolic disorders along with its phytochemical profiling for quality evaluation and validation of traditional claim. MATERIALS AND METHODS: The present study was carried out on hydroalcohol extract of dried leaf and fruit of Momordica dioica. In-vitro antioxidant potential using DPPH and Nitric oxide scavenging assay along with in-vitro enzyme inhibitory potential against α-amylase, α-glucosidase, and pancreatic lipase enzymes was studied. The bioactive metabolites were identified from the most potent bioactive extract by analysis with LC-QTOF-MS and also studied their role to lessen the metabolic related disorder through in-silico approaches. RESULTS: The results confirmed that the fruit extract is more active to possess antioxidant and prominent enzyme inhibition potential compared to the leaf. Sixteen identified metabolites in M. dioica Roxb. fruits may be responsible for the therapeutic potential related to metabolic related disorder. The in-silico study of the identified phytomolecules against α-amylase, α-glucosidase and pancreatic lipase showed significant docking scores ranging from -9.8 to -5.5, -8.3 to -4.8 and -8.3 to -6 respectively. CONCLUSION: The current study illustrated that M. dioica Roxb., a traditionally important plant is potential against metabolic related disorders. Phytocomponents present in the fruit extract may be responsible for antioxidant as well as the enzymes' inhibitory potential. Thus, fruits of M. dioica Roxb. will be useful as alternative therapeutics for treatment of hyperlipidemia, hyperglycemia and related metabolic disorders.

Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c).

BACKGROUND: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India. AIMS: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c). METHODS: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model. RESULTS: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal. CONCLUSION: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

Quantification of cucurbitacin E in different varieties of melon (Cucumis melo L.) fruit through validated RP-HPLC method.

The different varieties of melons (Cucumis melo L.) have been used in various traditional systems of medicine for decades to treat different ailments, including inflammation, cancer, cardiovascular, diabetes, edema, etc. The present study was designed for the quantification of cucurbitacin E in five different varieties of melon fruit through a validated RP-HPLC method. A solvent system is being optimized with a 70:30 (v/v) ratio of acetonitrile: water (1% glacial acetic acid) at a 1 mL/min flow rate and scanning spectrum (λmax) of 230 nm. A calibration curve for standard cucurbitacin E was generated and found to be linear (1-100 µg/mL). The variation of cucurbitacin E content among five different varieties of melon fruits is 0.0129% w/w- 0.231% w/w. This precise and reproducible method may be beneficial in addressing the quality-related aspects of medicinal food plants of Cucurbitaceae and its derived products or formulations.

Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications.

BACKGROUND: The worldwide corona virus disease outbreak, generally known as COVID-19 pandemic outbreak resulted in a major health crisis globally. The morbidity and transmission modality of COVID-19 appear more severe and uncontrollable. The respiratory failure and following cardiovascular complications are the main pathophysiology of this deadly disease. Several therapeutic strategies are put forward for the development of safe and effective treatment against SARS-CoV-2 virus from the pharmacological view point but till date there are no specific treatment regimen developed for this viral infection. PURPOSE: The present review emphasizes the role of herbs and herbs-derived secondary metabolites in inhibiting SARS-CoV-2 virus and also for the management of post-COVID-19 related complications. This approach will foster and ensure the safeguards of using medicinal plant resources to support the healthcare system. Plant-derived phytochemicals have already been reported to prevent the viral infection and to overcome the post-COVID complications like parkinsonism, kidney and heart failure, liver and lungs injury and mental problems. In this review, we explored mechanistic approaches of herbal medicines and their phytocomponenets as antiviral and post-COVID complications by modulating the immunological and inflammatory states. STUDY DESIGN: Studies related to diagnosis and treatment guidelines issued for COVID-19 by different traditional system of medicine were included. The information was gathered from pharmacological or non-pharmacological interventions approaches. The gathered information sorted based on therapeutic application of herbs and their components against SARSCoV-2 and COVID-19 related complications. METHODS: A systemic search of published literature was conducted from 2003 to 2021 using different literature database like Google Scholar, PubMed, Science Direct, Scopus and Web of Science to emphasize relevant articles on medicinal plants against SARS-CoV-2 viral infection and Post-COVID related complications. RESULTS: Collected published literature from 2003 onwards yielded with total 625 articles, from more than 18 countries. Among these 625 articles, more than 95 medicinal plants and 25 active phytomolecules belong to 48 plant families. Reports on the therapeutic activity of the medicinal plants belong to the Lamiaceae family (11 reports), which was found to be maximum reported from 4 different countries including India, China, Australia, and Morocco. Other reports on the medicinal plant of Asteraceae (7 reports), Fabaceae (8 reports), Piperaceae (3 reports), Zingiberaceae (3 reports), Ranunculaceae (3 reports), Meliaceae (4 reports) were found, which can be explored for the development of safe and efficacious products targeting COVID-19. CONCLUSION: Keeping in mind that the natural alternatives are in the priority for the management and prevention of the COVID-19, the present review may help to develop an alternative approach for the management of COVID-19 viral infection and post-COVID complications from a mechanistic point of view.

Therapeutic importance of Cucurbitaceae: A medicinally important family.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants of Cucurbitaceae family consist of several edible fruits and vegetables consumed worldwide since ancient times. The plants of this family have played an essential role in the ethnopharmacological as well as traditional medicinal system globally and their evidence is well established in several traditional literatures. Various plant parts have been used to treat several human ailments viz. Pandu (anemia), Pliharoga (splenomegaly), Sopha (inflammation), Gulma (tumor growth), Adhmana (indigestion. acidity), Garavisa (poisoning) etc. AIM OF THE REVIEW: This review article aims to systematically document and bridge scientific evidences with the ethnopharmacological, ethnoveterinary and folklore claims along with the therapeutic efficacy with mechanism of action found in different literature, books, and scientific articles belonging to the Cucurbitaceae family. MATERIALS AND METHODS: To construct the manuscript a comprehensive literature review was done based on the information collected from Ayurvedic Pharmacopoeia of India; books, research articles and databases such as ScienceDirect, Wiley Online Library, SciFinder, Scopus, Springer, Google Scholar, Web of Science, ACS Publications and PubMed. RESULTS: The plants of Cucurbitaceae family are rich in phytochemicals like terpenoids, glycosides, alkaloids, saponins, tannins, steroids, etc., responsible for the therapeutic effect. Various parts of these plants such as leaves, stems, flowers, fruits, seeds, roots etc. exhibit a plethora of pharmacological activity viz. hypolipidemic, antihyperglycemic, anticancer, antimicrobial, analgesic, anti-inflammatory, anti-stress and immunomodulatory activities. Also, in-vitro and in-vivo reports suggest strong inhibitory potential against α-glucosidase, α-amylase, lipase, carbonic anhydrase enzyme along with antioxidant, anti-inflammatory, antidiabetic, anti-tumor, antifungal, etc. Furthermore many reports suggest these plants are beneficial for nutritional, economical and ethnoveterinary uses. CONCLUSIONS: The current review enlightens the therapeutic potential of the gourd family, comprising of the geographical origins, morphology, phytochemistry, ethnopharmacology, ethnoveterinary, nutritional importance, therapeutic benefits, safety, efficacy and related aspects. The phytochemical and pharmacological potential indicated will popularize this family as a potential source of novel therapeutic agents and functional foods. This study will help to validate the therapeutic claims of several ethnomedicinal uses of this plant family. Furthermore the Cucurbitaceae family needs to be evaluated based on the combine approaches of chemoprofiling and bioexploration to develop the concept of food as medicine for the development of new generation therapeutics leading to the human wellness.

Lagenaria siceraria and it's bioactive constituents in carbonic anhydrase inhibition: A bioactivity guided LC-MS/MS approach.

INTRODUCTION: Lagenaria siceraria, is a popular food plant among Indians, contains a large number of phenolic compounds with several medicinal benefits, mentioned in Indian System of Medicine (ISM). OBJECTIVES: To investigate the carbonic anhydrase inhibitory potential and inhibitory mechanism of the most potent fraction of L. siceraria fruits. MATERIALS AND METHODS: The extract and fraction of dried fruit of L. siceraria screened for their in vitro carbonic anhydrase II (bCA II) inhibitory activity. The active fraction was purified by using flash chromatography. The bioactive compounds were identified and quantified through liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) and reverse-phase high-performance liquid chromatography (RP-HPLC). Finally, the underlying carbonic anhydrase inhibitory mechanism of the compounds was explained by enzyme kinetics and molecular docking study. RESULTS: The LC-QTOF-MS based identification of the most active fraction revealed the presence of phenolic compounds. The results of the enzyme inhibition assay revealed that coniferyl alcohol, ferulic acid and p-Coumaric acid inhibited bCA II activity [half maximal inhibitory concentration (IC50 ) value range of 80 to 250 µM) in a dose dependent manner. The kinetics study of enzyme inhibition revealed that p-Coumaric acid binds to the enzyme competitively whereas the non-competitive type of inhibition was observed for ferulic acid and coniferyl alcohol. The molecular docking study explored the interaction mechanism of phenolic compounds at the active site of bCA II. CONCLUSION: The present research led us to conclude that, the phenolic compounds from L. siceraria serve as major contributors for carbonic anhydrase inhibition, which could play a useful role in the management of oedema, hypertension, obesity and related metabolic disorders.

LC-QTOF-MS-based metabolite profiling and evaluation of α-glucosidase inhibitory kinetics of Coccinia grandis fruit.

Coccinia grandis is an important food crop of the Cucurbitaceae family, widely used for culinary purposes in India. It is reported to possess hypoglycemic, hypolipidemic and antioxidant activities. The current study was aimed to explore the inhibition kinetics as well as major constituents of the active fraction of C. grandis against α-glucosidase. The kinetic study was performed through spectrophotometric assay, with p-nitrophenyl-α-d-glucopyranoside as a substrate with varying concentrations. An in vitro antioxidant study was performed by DPPH assay. In addition, UPLC-QTOF-MS analysis was carried out for metabolite profiling of the bioactive fraction of C. grandis. The results showed that the difference between the α-glucosidase inhibitory activity of the ethyl acetate fraction of C. grandis (EFCG) (IC50 2.43 ± 0.27 mg/ml), and standard inhibitor, acarbose (2.08 ± 0.19 mg/ml), was not statistically significant at a P-value of 0.05. The enzyme kinetics confirmed the inhibition mode in a mixed manner. The EFCG also showed the highest antioxidant activity (101.74 ± 1.95 µg/ml) among all of the fractions. A significant correlation between antioxidant and α-glucosidase inhibitory activity of EFCG was observed. The LC-QTOF-MS study of the EFCG putatively identified 35 metabolites, which may be responsible for its antioxidant and α-glucosidase inhibitory properties. Thus, C. grandis fruits can serve as a functional food to address diabetes-related disorders associated with α-glucosidase.