Repurposing of existing antibiotics for the treatment of diabetes mellitus.

Proline specific serine protease enzyme, dipeptidyl peptidase IV (DPP-4) has become a promising target for diabetes, as it stops glucagon-like peptide 1 (GLP-1) from becoming inactive, resulting in higher levels of active GLP-1. This lowers glucose levels by increasing insulin secretion and decreasing glucagon secretion. DPP-4 is also linked to a higher BMI and a 0.7 to 1% reduction in HbA1c. Currently available DPP-4 inhibitor drugs showed less promising anti-diabetic activity as this class associated with many side effects due to non-selectivity and therefore searching on more potent DPP-4 inhibitors are still ongoing. In our present study, we investigate the inhibition of DPP-4 through a series of antibiotic compounds which were previously reported to be used in diabetic foot infections and compared with existing DPP-4 inhibitors. To obtain this objective, three-dimensional crystal structure of DPP-4 was retrieved from the protein data bank (PDB id: 1 × 70). A systematic computational method combining molecular docking, MM-GBSA binding energy calculation, MD simulations, MM-PBSA binding free energy calculations and ADME were used to find best DPP-4 inhibitor. Molecular docking results revealed that clindamycin has a higher affinity towards the catalytic sides of DPP-4 and built solid hydrophobic and polar interactions with the amino acids involved in the binding region of DPP-4, such as S1 subsite, S2 subsite and S2 extensive subsite. MD simulations results showed clindamycin as potent virtual hit and suggested that it binds with DPP-4 in competitive manner, which virtually indicate that besides antibiotic activity clindamycin has anti-diabetic activity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-021-00118-6.

Ziziphus oenoplia Mill.: A Systematic Review on Ethnopharmacology, Phytochemistry and Pharmacology of an Important Traditional Medicinal Plant.

BACKGROUND: Ziziphus oenoplia Mill. (Family- Rhamnaceae) an important shrub, often found throughout the hot regions of tropical Asia and northern Australia, is commonly well known as Jackal jujube in English. It is a folk herbal medicine used as an abdominal pain killer and antidiarrhoeal agent. OBJECTIVE: The review aims to provide up-to-date information on the vernacular information, botanical characterization, distribution, ethnopharmacological uses, pharmacological activities, and chemical constituents of Z. oenoplia for possible exploitation of treatment for various diseases and to suggest future investigations. METHODS: This review was performed by studying online resources relating to Z. oenoplia and diverse resources, including scientific journals, books, and worldwide accepted databases from which information was assembled to accumulate significant information and relevant data in one place. RESULTS: Investigations on Z. oenoplia have been focused on its pharmacological activities, including its antimicrobial, antidiabetic, antihepatotoxic, antiulcer, antiplasmodial, anticancer, wound healing, anthelmintic, antioxidant, analgesic and antinociceptive, hypolipidemic activity, anti-inflammatory, immunomodulatory and antidiarrheal activities. Phytochemical studies resulted in the isolation of fatty acids, flavonoids, phenols, pentacyclic triterpenes, hydroxycarboxylic acids, aliphatic hydroxy ether, and cyclopeptide alkaloids. CONCLUSION: Most of the ethnopharmacological relevance of Z. oenoplia is justified, but more studies are needed. Further investigations are necessary to fully understand the mode of action of the active constituents and to exploit its preventive and therapeutic potentials.

GreenMolBD: Nature Derived Bioactive Molecules' Database.

BACKGROUND: One of the essential resources for developing new drugs are naturally derived biologically active lead compounds. Biomedical researchers and pharmaceutical companies are highly interested in these plant-derived molecules to develop the new drug. In this process, collective information of the plants and their phytoconstituents with different properties and descriptors would greatly benefit the researchers to identify the hit, lead or drug-like compound. AIM AND OBJECTIVE: Therefore, the work intended to develop a unique and dynamic database Green- MolBD to provide collective information regarding medicinal plants, such as their profile, chemical constituents, and pharmacological evidence. We also aimed to present information of phytoconstituents, such as in silico description, quantum, drugability and biological target information. METHODS: For data mining, we covered all accessible literature and books, and for in silico analysis, we employed a variety of well-known software and servers. The database is integrated by MySQL, HTML, PHP and JavaScript. RESULTS: GreenMolBD is a freely accessible database and searchable by keywords, plant name, synonym, common name, family name, family synonym, compound name, IUPAC name, InChI Key, target name, and disease name. We have provided a complete profile of individual plants and each compound's physical, quantum, drug likeliness, and toxicity properties (48 type's descriptor) using in silico tools. A total of 1846 associated targets related to 6,864 compounds already explored in different studies are also incorporated and synchronized. CONCLUSION: This is the first evidence-based database of bioactive molecules from medicinal plants specially grown in Bangladesh, which may help explore and foster nature-inspired rational drug discovery.

A Comprehensive Review on Linum usitatissimum Medicinal Plant: Its Phytochemistry, Pharmacology, and Ethnomedicinal Uses.

BACKGROUND: Linum usitatissimum or flax has been broadly utilized in numerous milieus worldwide as a primeval medicinal plant because of its health benefits in diverse types of diseases. OBJECTIVE: The objective of this review is to assemble the latest information on the botanical description, distribution, conventional uses, and biochemical constituents, along with the pharmacological activities and toxicity of flax. METHODS: For this purpose, data on Linum was accumulated from scientific journals, books, and worldwide acknowledged scientific databases via a library and electronic search. RESULTS: Phytochemical analysis showed that the major chemical constituents of L. usitatissimum are ω-3 fatty acid, phytoestrogenic-lignans (secoisolariciresinol diglucoside-SDG), phenols, flavonoids, sterols, proteins, antioxidants as well as various soluble and insoluble fibres. Among them, secoisolariciresinol diglucosides (SDG) are the major bioactive compounds of L. usitatissimum with prospective pharmacological accomplishments. Pure compounds and crude extracts isolated from L. usitatissimum exhibited significant anti-cancer, antioxidant, anti-microbial, anti-inflammatory, anti-obesity, antidiabetic, anti-diarrheal, anti-malarial, hepato-protective, reno-protective, immunosuppressive, antiarrhythmic, and cognitive effects. Studies indicated that the toxicological effect from the consumption of flaxseed is because of its cyanogenic glycosides, linatine, and cadmium, but the level does not seem to be adequately concentrated to contribute to any physiological impact. CONCLUSIONS: Further studies are expected to comprehend the detailed mode of action of its dynamic constituents as potent therapeutics and to completely reveal its preventive and healing potentials.

Phytochemistry, Traditional Uses and Pharmacological Properties of Enhydra fluctuans Lour: a Comprehensive Review.

BACKGROUND: Enhydra fluctuans Lour, a tropical herb, commonly known as helencha or harkuch, belongs to the family Asteraceae. It is an edible semi-aquatic herbaceous vegetable plant with serrate leaves and grows commonly in different parts of the world. Enhydra fluctuans possesses potential pharmacological role against inflammation, cancer, diarrhea, microbial infection, diabetes, etc. Aim: This review aims to provide the most current information on the botanical characterization, distribution, traditional uses, chemical constituents, as well as the pharmacological activities of Enhydra fluctuans Lour. MATERIALS AND METHODS: The recently updated information on Enhydra fluctuans was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library. All of the full-text articles and abstracts related to Enhydra were screened. The most important and relevant articles were carefully chosen for study in this review. RESULTS: Crude extracts and isolated compounds of Enhydra fluctuans Lour have been reported to be pharmacologically active against cytoprotective, analgesic and anti-inflammatory, antimicrobial, anticancer, antidiarrheal, antihelmintic, CNS depressant, hepatoprotective, thrombolytic, antidiabetic, antioxidant, phagocytic and cytotoxic, and neuroprotective potential activities. DISCUSSION: Phytochemical analysis from different studies has reported Germacranolide, Sesquiterpene lactone, Flavonoid, Essential oil, Steroid, Diterpenoid, Melampolide, Sesquiterpene lactone, and Isoflavone glycoside as major compounds of Enhydra fluctuans Lour. CONCLUSION: However, more research is needed to explore the mode of action of bioactive components of the plant and its therapeutic capabilities.

A Review of Saurauia roxburghii Wall. (Actinidiacaea) as a Traditional Medicinal Plant, Its Phytochemical Study and Therapeutic Potential.

Saurauia roxburghii Wall. is an interesting plant, found growing chiefly along the eastern and south-eastern countries of Asia. The various ethnic groups of these regions use the plant as a medication for relieving a wide spectrum of diseases and conditions, including indigestion, boils, fever, gout, piles, eczema, asthma, ulcers, bronchitis, epilepsy, and hepatitis B. This review aims to appraise the vernacular information, botanical characterization, geographical distribution, traditional uses, phytochemistry, and pharmacological activities of S. roxburghii as well as to conduct a critical analysis on the findings. To understand the therapeutic potential and provide an overall idea about the ethnomedicinal practices, phytochemistry, and pharmacological activities of S. roxburghii, relevant information was collected via a library and electronic search of online journals, books, and reputed databases. Phytochemical examination revealed the presence of alkaloids, glycosides, O-glycosides, flavonoids, carbohydrates, saponins, steroids, reducing sugars, tannins, phlobatannins, and triterpenoids. The sterols were identified as Stigmasterol and beta-Sitosterol. The triterpenes were found to be Ursolic acid, Corosolic acid, Maslinic acid, 24-Hydroxy corosolic acid, 3b,7b,24-trihydroxy-urs-12-en-28-oic acid, Oleanolic acid, beta-Amyrin, cis-3-O-p-Hydroxycinnamoyl ursolic acid, trans-3-O-p- Hydroxycinnamoyl ursolic acid, and 7,24-dihydroxyursolic acid. Several in-vivo and in-vitro tests revealed anti-bacterial, anti-cancer, anti-diabetic, anti-oxidant, and anti-viral activities of the plant leaves. Detailed analysis of the information collected on S. roxburghii suggested some promising leads for future drug development. However, many scientific gaps were found in the study of this and further extensive investigation is needed to fully understand the mechanism of action of the active constituents and exploit its therapeutic promises.

Effects of microclimate and human parameters on outdoor thermal sensation in the high-density tropical context of Dhaka.

A thermal comfort questionnaire survey was carried out in the high-density, tropical city Dhaka. Comfort responses from over 1300 subjects were collected at six different sites, alongside meteorological parameters. The effect of personal and psychological parameters was examined in order to develop predictive models. Personal parameters included gender, age, activity, profession-type (indoor or outdoor-based), exposure to air-conditioned space and sweat-levels. Psychological parameters, such as 'the reason for visiting the place' and 'next destination is air-conditioned', had statistically significant effects on thermal sensation. Other parameters, such as 'body type', 'body exposure to sun', 'time living in Dhaka', 'travelling in last_30 min', and 'hot food' did not have any significant impact. Respondents' humidity, wind speed and solar radiation sensation had profound impacts and people were found willing to adjust to the thermal situations with adaptive behaviour. Based on actual sensation votes from the survey, empirical models are developed to predict outdoor thermal sensation in the case study areas. Ordinal linear regression techniques are applied for predicting thermal sensation by considering meteorological and personal conditions of the field survey. The inclusion of personal and weather opinion factors produced an improvement in models based on meteorological factors. The models were compared with the actual thermal sensation using the cross-tabulation technique. The predictivity of the three models (meteorological, thermos-physiological and combined parameter) as expressed by the gamma coefficient were 0.575, 0.636 and 0.727, respectively. In all three models, better predictability was observed in the 'Slightly Warm' (71% in meteorological model) and 'Hot' (64.9% in combined parameter model) categories-the most important ones in a hot-humid climate.