Waste to Medicine: Evidence from Computational Studies on the Modulatory Role of Corn Silk on the Therapeutic Targets Implicated in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and/or defective insulin production in the human body. Although the antidiabetic action of corn silk (CS) is well-established, the understanding of the mechanism of action (MoA) behind this potential is lacking. Hence, this study aimed to elucidate the MoA in different samples (raw and three extracts: aqueous, hydro-ethanolic, and ethanolic) as a therapeutic agent for the management of T2DM using metabolomic profiling and computational techniques. Ultra-performance liquid chromatography-mass spectrometry (UP-LCMS), in silico techniques, and density functional theory were used for compound identification and to predict the MoA. A total of 110 out of the 128 identified secondary metabolites passed the Lipinski's rule of five. The Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis revealed the cAMP pathway as the hub signaling pathway, in which ADORA1, HCAR2, and GABBR1 were identified as the key target genes implicated in the pathway. Since gallicynoic acid (-48.74 kcal/mol), dodecanedioc acid (-34.53 kcal/mol), and tetradecanedioc acid (-36.80 kcal/mol) interacted well with ADORA1, HCAR2, and GABBR1, respectively, and are thermodynamically stable in their formed compatible complexes, according to the post-molecular dynamics simulation results, they are suggested as potential drug candidates for T2DM therapy via the maintenance of normal glucose homeostasis and pancreatic ß-cell function.

Cheminformatics identification of modulators of key carbohydrate-metabolizing enzymes from C. cujete for type-2 diabetes mellitus intervention.

Purpose: The therapeutic use of oral hypoglycaemic agents in the management of type-2 diabetes mellitus (T2DM) is without adverse effects; thus, calls for alternative and novel candidates from natural products in medicinal plants. Method: The study explored molecular docking and molecular dynamics (MD) simulation approaches to identify key antidiabetic metabolites from Crescentia cujete. Results: Molecular docking results identified four and/or five best compounds against each target enzyme (alpha-glucosidase, dipeptidyl peptidase-IV, aldose reductase, and protein tyrosine phosphatase-1B (PTP-1B)) implicated in diabetes. The resulting complexes (except against PTP-1B) had higher docking scores above respective standards (acarbose, Diprotin A, ranirestat). The MD simulation results revealed compounds such as benzoic acid (-48.414 kcal/mol) and phytol (-45.112 kcal/mol) as well as chlorogenic acid (-42.978 kcal/mol) and naringenin (-31.292 kcal/mol) had higher binding affinities than the standards [acarbose (-28.248 kcal/mol), ranirestat (-21.042 kcal/mol)] against alpha-glucosidase and aldose reductase, respectively while Diprotin A (-45.112 kcal/mol) and ursolic acid (-18.740 kcal/mol) presented superior binding affinities than the compounds [luteolin (-41.957 kcal/mol and naringenin (-16.518 kcal/mol)] against DPP-IV and PTP-1B respectively. Conclusion: While isoflavone (alpha-glucosidase), xylocaine (DPP-IV), luteolin (aldose reductase,) and chlorogenic acid (PTP-1B) were affirmed as the best inhibitors of respective enzyme targets, luteolin, and chlorogenic acid may be suggested and proposed as probable candidates against T2DM and related retinopathy complication based on their structural stability, compactness and affinity for three (DPP-IV, aldose reductase, and PTP-1B) of the four targets investigated. Further studies are warranted in vitro and in vivo on the antihyperglycaemic effects of these drug candidates. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01249-7.

A review of indigenous knowledge and ethnopharmacological significance of African Copaiba Balsam Tree, Daniellia oliveri (Fabaceae).

Daniellia oliveri has found its indigenous relevance in the management of diseases including but not limited to diabetes mellitus, tuberculosis, fever, ulcers, pain, worm manifestation, pneumonia, skin ailments, infectious diseases, sickle cell anaemia, hence, a review of its indigenous knowledge, ethnopharmacological and nutritional benefits was undertaken. Information used for the review was sourced from popular scientific databases (Google Scholar, PubMed, Science Direct, Web of Science, BioMed Central, JSTOR, African Plant, Global Biodiversity Information and others), conference proceedings, dissertations or theses, chapters in books, edited books, and journal collections. The materials obtained from 121 scientific documents targeting majorly between 1994 and 2023 established the presence of major secondary metabolites (such as polyphenols, flavonoids, saponins, alkaloids, etc.), minerals (e.g., sodium, potassium, phosphorus, selenium, calcium, magnesium, etc.), vitamins (beta-carotene, thiamine, riboflavin, niacin, ascorbic acid, etc.), and nutrients (crude protein, moisture, dry matter, ether, carbohydrates, and energy). Literature also lent credence to the preliminary safety profiles of the plant and its pharmacological potentials as analgesic, antinociceptive, antioxidant, antidiabetic, antidiarrhoeal, anthelmintic, anti-inflammatory, antimelanogenesis, antimicrobial, antiplasmodial, antisickling, cardiotoxic, cytotoxic, and neuroprotective agents. While the review is majorly limited to Africa particularly western countries (such as Nigeria, Burkina Faso, Mali, Ghana, Togo, and Benin) and the plant is found to be largely underutilized, it is evident that limited information exists on the in vivo pharmacological evaluation, bioactive compounds identification, and there is a lack of preclinical and clinical trials for possible drug development. Based on the aforementioned, it is hoped that further research studies geared toward providing insights into the established grey areas (such as traditional use investigation, targeted or assay-guided compounds identification, and preclinical and clinical studies) are necessary in order to fully explore the therapeutic, nutritional, and economic benefits of the plant.

Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy.

Recently, dipeptidyl peptidase-IV (DPP-IV) has become an effective target in the management of type-2 diabetes mellitus (T2D). The study aimed to determine the efficacy of shikimate pathway-derived phenolic acids as potential DPP-IV modulators in the management of T2D. The study explored in silico (molecular docking and dynamics simulations) and in vitro (DPP-IV inhibitory and kinetics assays) approaches. Molecular docking findings revealed chlorogenic acid (CA) among the examined 22 phenolic acids with the highest negative binding energy (-9.0 kcal/mol) showing a greater affinity for DPP-IV relative to the standard, Diprotin A (-6.6 kcal/mol). The result was corroborated by MD simulation where it had a higher affinity (-27.58 kcal/mol) forming a more stable complex with DPP-IV than Diprotin A (-12.68 kcal/mol). These findings were consistent with in vitro investigation where it uncompetitively inhibited DPP-IV having a lower IC50 (0.3 mg/mL) compared to Diprotin A (0.5 mg/mL). While CA showed promising results as a DPP-IV inhibitor, the findings from the study highlighted the significance of medicinal plants particularly shikimate-derived phenolic compounds as potential alternatives to synthetic drugs in the effective management of T2DM. Further studies, such as derivatisation for enhanced activity and in vivo evaluation are suggested to realize its full potential in T2D therapy.

A Review of the Phytochemistry, Ethnobotany, Toxicology, and Pharmacological Potentials of Crescentia cujete L. (Bignoniaceae).

Crescentia cujete is an economical and medicinal plant of wide indigenous uses including hypertension, diarrhea, respiratory ailments, stomach troubles, infertility problems, cancer, and snakebite. Despite these attributes, C. cujete is largely underutilized, notwithstanding the few progresses made to date. Here, we reviewed the available findings on the ethnobotany, phytochemistry, toxicology, and pharmacology, as well as other economic benefits of the plant. The information on the review was gathered from major scientific databases (Google scholar, Scopus, Science Direct, Web of Science, PubMed, Springer, and BioMed Central) using journals, books, and/or chapters, dissertations, and conference proceedings. The review established the antidiabetic, antioxidant, acaricidal, antibacterial, anti-inflammatory, anthelmintic, antivenom, wound healing, neuroprotection, antiangiogenic, and cytotoxic properties from aqueous and organic (particularly ethanol) aerial parts attributed to several secondary metabolites such as flavonoids, alkaloids, saponins, tannins, phenols, cardiac glycosides, phytosterols, reducing sugar, and volatile oils. Economically, the fruit hard outer shell found applications as musical tools, tobacco pipes, bowls, food containers, and bioethanol production. While most of the current studies on C. cujete are mainly from Asia and South America (Philippines, Bangladesh, India, etc.), part of the persistence challenge is lack of comprehensive data on the plant from in vivo pharmacological studies of its already characterized compounds for probable clinical trials toward drug discovery. Consequently, upon this, modern and novel translational studies including the concept of '-omics' are suggested for studies aiming to outfit more comprehensive data on its therapeutic profiles against pathological markers of diseases and to fully explore its economic benefits.

Isolation of flavonoids from Musa acuminata Colla (Simili radjah, ABB) and the in vitro inhibitory effects of its leaf and fruit fractions on free radicals, acetylcholinesterase, 15-lipoxygenase, and carbohydrate hydrolyzing enzymes.

Musa species are used traditionally for the management of many diseases. The study evaluated and compared anticholinesterase, anti-inflammatory, antioxidant, and antidiabetic activities of Musa acuminata (Simili radjah, ABB) fruits and leaves fractions and characterized the bioactive compounds using HPTLC-HRMS and NMR. Leaf fractions gave the higher biological activities than the fruit. Ethyl acetate fraction of the leaf had the highest total phenolic content (911.9 ± 1.7 mg GAE/g) and highest 2,2-diphenyl-1-picrylhydrazyl (DPPH· ) scavenging activity (IC50, 9.0 ± 0.4 µg/ml). It also gave the most effective inhibition of acetylcholinesterase (IC50, 404.4 ± 8.0 µg/ml) and α-glucosidase (IC50, 4.9 ± 1.6 µg/ml), but a moderate α-amylase inhibition (IC50, 444.3 ± 4.0 µg/ml). The anti-inflammatory activity of n-butanol (IC50, 34.1 ± 2.6 µg/ml) and ethyl acetate fractions (IC50 , 43.1 ± 11.3 µg/ml) of the leaf were higher than the positive control, quercetin (IC50 , 54.8 ± 17.1 µg/ml). Kaempferol-3-O-rutinoside and quercetin-3-O-rutinoside (rutin) were identified as the bioactive compounds with antioxidant and antidiabetic activities from the ethyl acetate fraction of M. acuminata leaf. PRACTICAL APPLICATIONS: All parts of Musa acuminata are known to be useful ethnomedicinally even as food. The leaves are mostly used to serve food and used for wrapping purposes. However, this study concluded that M. acuminata leaf is rich in bioactive flavonoids such as kaempferol-3-O-rutinoside and rutin, with relatively high antioxidative, antidiabetic, and anti-inflammatory activities. Therefore, aside the fact that the leaves can serve as potential drug leads for pharmaceutical industries, it can also be embraced in the food sector to produce supplements and/or nutraceuticals in the management of Alzheimer's, diabetes and other inflammatory diseases.

A Review of Plants Used in South African Traditional Medicine for the Management and Treatment of Hypertension.

South Africa contains 9% of the world's higher plants, and despite its rich biodiversity, it has one of the highest prevalence of hypertension in Africa. This review provides information on medicinal plants embraced in South Africa for hypertension management, with the aim of reporting pharmacological information on the indigenous use of these plants as antihypertensives. This review not only focuses on the activity of antihypertensive medicinal plants but also reports some of its phytochemical constituents and other ethnopharmacological and therapeutic properties. Information obtained from scientific and or unpublished databases such as Science Direct, PubMed, SciFinder, JSTOR, Google Scholar, Web of Science, and various books revealed 117 documented antihypertensive plant species from 50 families. Interestingly, Asteraceae topped the list with 16 species, followed by Fabaceae with 8 species; however, only 25% of all plant species have demonstrated antihypertensive effects originating from both in vitro and in vivo studies, lending credence to their folkloric use. Only 11 plant species reportedly possess antihypertensive properties in animal models, with very few species subjected to analytical processes to reveal the identity of their bioactive antihypertensive compounds. In this review, we hope to encourage researchers and global research institutions (universities, agricultural research councils, and medical research councils), particularly those showing an interest in natural products, for the need for concerted efforts to undertake more studies aimed at revealing the untapped potential of these plants. These studies are very important for the development of new pharmaceuticals of natural origin useful for the management of hypertension.

Antidiabetic Medicinal Plants Used by the Basotho Tribe of Eastern Free State: A Review.

Diabetes mellitus (DM) belongs to the group of five leading important diseases causing death globally and remains a major health problem in Africa. A number of factors such as poverty, poor eating habit, and hormonal imbalance are responsible for the occurrence of the disease. It poses a major health challenge in Africa continent today and the prevalence continues to increase at an alarming rate. Various treatment options particularly the usage of herbs have been effective against diabetes because they have no adverse effects. Interestingly, South Africa, especially the Basotho tribe, is blessed with numerous medicinal plants whose usage in the treatment of DM has been effective since the conventional drugs are expensive and often unaffordable. The present study attempted to update the various scientific evidence on the twenty-three (23) plants originating from different parts of the world but widely used by the Sotho people in the management of DM. Asteraceae topped the list of sixteen (16) plant families and remained the most investigated according to this review. Although limited information was obtained on the antidiabetic activities of these plants, it is however anticipated that government parastatals and scientific communities will pay more attention to these plants in future research.

Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats.

The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe.