Development and Characterization of Novel Biopolymer Derived from Abelmoschus esculentus L. Extract and Its Antidiabetic Potential

Abelmoschus esculentus (Okra) is an important vegetable crop, widely cultivated around the world due to its high nutritional significance along with several health benefits. Different parts of okra including its mucilage have been currently studied for its role in various therapeutic applications. Therefore, we aimed to develop and characterize the okra mucilage biopolymer (OMB) for its physicochemical properties as well as to evaluate its in vitro antidiabetic activity. The characterization of OMB using Fourier-transform infrared spectroscopy (FT-IR) revealed that okra mucilage containing polysaccharides lies in the bandwidth of 3279 and 1030 cm⁻¹, which constitutes the fingerprint region of the spectrum. In addition, physicochemical parameters such as percentage yield, percentage solubility, and swelling index were found to be 2.66%, 96.9%, and 5, respectively. A mineral analysis of newly developed biopolymers showed a substantial amount of calcium (412 mg/100 g), potassium (418 mg/100 g), phosphorus (60 mg/100 g), iron (47 mg/100 g), zinc (16 mg/100 g), and sodium (9 mg/100 g). The significant antidiabetic potential of OMB was demonstrated using α-amylase and α-glucosidase enzyme inhibitory assay. Further investigations are required to explore the newly developed biopolymer for its toxicity, efficacy, and its possible utilization in food, nutraceutical, as well as pharmaceutical industries.     

Synthesis and Characterization of an Analgesic Potential Conotoxin Lv32.1

In our work of screening analgesic peptides from the conotoxin libraries of diverse Conus species, we decoded a peptide sequence from Conus lividus and named it Lv32.1 (LvXXXIIA). The folding conditions of linear Lv32.1 on buffer, oxidizing agent, concentration of GSH/GSSG and reaction time were optimized for a maximum yield of (34.94 ± 0.96)%, providing an efficient solution for the synthesis of Lv32.1. Its disulfide connectivity was identified to be 1–3, 2–6, 4–5, which was first reported for the conotoxins with cysteine framework XXXII and different from the common connectivities established for conotoxins with six cysteines. The analgesic effect of Lv32.1 was determined by a hot plate test in mice. An evident increase in the pain threshold with time illustrated that Lv32.1 exhibited analgesic potency. The effects on Na_v1.8 channel and α9α10 nAChR were detected, but weak inhibition was observed. In this work, we highlight the efficient synthesis, novel disulfide linkage and analgesic potential of Lv32.1, which laid a positive foundation for further development of conotoxin Lv32.1 as an analgesic candidate.     

Synthesis of Hydroxypropyltrimethyl Ammonium Chitosan Derivatives Bearing Thioctate and the Potential for Antioxidant Application

Hydroxypropyltrimethyl ammonium chloride chitosan (HACC) is one of the most important water-soluble chitosan derivatives; its derivatives have gained growing attention due to their potential biomedical applications. Here, hydroxypropyltrimethyl ammonium chitosan derivatives bearing thioctate (HACTs), with different degrees of substitution of thioctate, were prepared using HACC and α-lipoic acid as the reaction precursors, using an ion exchange method. The structural characteristics of the synthesized derivatives were confirmed by FTIR, ¹H NMR, and ¹³C NMR spectroscopy. In addition, their antioxidant behaviors were also investigated in vitro by the assays of reducing power, and scavenging activities against hydroxyl radicals and DPPH radicals. The antioxidant assay indicated that HACTs displayed strong antioxidant activity compared with HACC, especially in terms of reducing power. Besides, the antioxidant activities of the prepared products were further enhanced with the increase in the test concentration and the degrees of substitution of thioctate. At the maximum test concentration of 1.60 mg/mL, the absorbance value at 700 nm of HACTs, under the test conditions, was 4.346 ± 0.296, while the absorbance value of HACC was 0.041 ± 0.007. The aforementioned results support the use of HACTs as antioxidant biomaterials in food and the biomedical field.     

Barbeya oleoides Leaves Extracts: In Vitro Carbohydrate Digestive Enzymes Inhibition and Phytochemical Characterization

This study investigated the in vitro inhibitory potential of different solvent extracts of leaves of Barbeya oleoides on key enzymes related to type 2 diabetes mellitus (α-glucosidase and α-amylase) in combination with an aggregation assay (using 0.01% Triton X-100 detergent) to assess the specificity of action. The methanol extract was the most active in inhibiting α-glucosidase and α-amylase, with IC₅₀ values of 6.67 ± 0.30 and 25.62 ± 4.12 µg/mL, respectively. However, these activities were significantly attenuated in the presence of 0.01% Triton X-100. The chemical analysis of the methanol extract was conducted utilizing a dereplication approach combing LC-ESI-MS/MS and database searching. The chemical analysis detected 27 major peaks in the negative ion mode, and 24 phenolic compounds, predominantly tannins and flavonol glycosides derivatives, were tentatively identified. Our data indicate that the enzyme inhibitory activity was probably due to aggregation-based inhibition, perhaps linked to polyphenols.     

The Glycemic Control Potential of Some Amaranthaceae Plants,with Particular Reference to In Vivo Antidiabetic Potential of Agathophora alopecuroides

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC₅₀ 117.9 µg/mL noting better activity than Acarbose (IC₅₀ 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC₅₀ 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.     

Biological Properties of Latex,Aqueous Extracts and Bee Products of Euphorbia officinarum L.: A Short Review

Euphorbia officinarum L. is a Moroccan endemic plant known as “Tikiout” and “Daghmus” that can also be found in Mauritania, Western Sahara, and Algeria. In the present review, “Euphorbia officinarum”, “metabolites” “hemisynthesis” were the keywords used for the research in the Web search engine Google Scholar and in the database Web of Science. Triterpenes, phytosterols and ingol diterpenes were isolated and identified in the latex of Moroccan E. officinarum. More than sixty triterpenes were obtained by hemisynthesis from natural triterpenes. Some of these derivatives had insecticidal and antimicrobial activity (phytopathogenic bacteria). The total phenol content and the antioxidant and anti-α-glucosidase activities were dependent on the time and temperature of extractions and also on the plant solvent ratio. The antioxidant activity of monofloral honey of E. officinarum origin was attributed to the phenol fraction (this fraction, previously isolated from honey samples, had better activity than the entire honey).     

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies

Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatography–mass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by β-(E)-ocimene (11.80%), D-limonene (8.08%), β-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC₅₀ value of 38.15 ± 2.09 µg/mL. In addition, it effectively inhibited acetylcholinesterase with an IC₅₀ value of 32.9 ± 2.1 µg/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC₅₀ values of 57.80 ± 3.30 and 274.03 ± 12.37 µg/mL, respectively. The molecular docking studies revealed that (E)-β-caryophyllene, one of the major compounds, achieved the best docking scores of −6.75, −5.61, and −7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose.     

Synthesis of Novel α-Trifluorothioanisole Derivatives Containing Phenylpyridine Moieties with Herbicidal Activity

To discover novel herbicidal compounds with favorable activity, a range of phenylpyridine-moiety-containing α-trifluorothioanisole derivatives were designed, synthesized, and identified via NMR and HRMS. Preliminary screening of greenhouse-based herbicidal activity revealed that compound 5a exhibited >85% inhibitory activity against broadleaf weeds Amaranthus retroflexus, Abutilon theophrasti, and Eclipta prostrate at 37.5 g a.i./hm², which was slightly superior to that of fomesafen. The current study suggests that compound 5a could be further optimized as an herbicide candidate to control various broadleaf weeds.     

The Nutritional and Antioxidant Potential of Artisanal and Industrial Apple Vinegars and Their Ability to Inhibit Key Enzymes Related to Type 2 Diabetes In Vitro

The main objective of the current study was to determine the physicochemical properties, antioxidant activities, and α-glucosidase and α-amylase inhibition of apple vinegar produced by artisanal and industrial methods. Apple vinegar samples were analyzed to identify their electrical conductivity, pH, titratable acidity, total dry matter, Brix, density, mineral elements, polyphenols, flavonoids, and vitamin C. The antioxidant activity of apple vinegar samples was evaluated using two tests, total antioxidant capacity (TAC) and DPPH radical scavenging activity. Finally, we determined α-glucosidase and α-amylase inhibitory activities of artisanal and industrial apple vinegar. The results showed the following values: pH (3.69–3.19); electrical conductivity (2.81–2.79 mS/cm); titratable acidity (3.6–5.4); ash (4.61–2.90); °Brix (6.37–5.2); density (1.02476–1.02012), respectively, for artisanal apple vinegar and industrial apple vinegar. Concerning mineral elements, potassium was the most predominant element followed by sodium, magnesium, and calcium. Concerning bioactive compounds (polyphenols, flavonoids, and vitamin C), the apple vinegar produced by the artisanal method was the richest sample in terms of bioactive compounds and had the highest α-glucosidase and α-amylase inhibition. The findings of this study showed that the quality and biological activities of artisanal apple vinegar were more important than industrial apple vinegar.     

In Vitro Inhibitory Effects of Viburnum opulus Bark and Flower Extracts on Digestion of Potato Starch and Carbohydrate Hydrolases Activity

One of the effective treatments for diabetes is to reduce and delay the absorption of glucose by inhibition of α-amylase and α-glucosidase in the digestive tract. Currently, there is a great interest in natural inhibitors from various part of plants. In the present study, the phenolic compounds composition of V. opulus bark and flower, and their inhibitory effects on in vitro potato starch digestion as well as on α-amylase and α-glucosidase, have been studied. Bark and flower phenolic extracts reduced the amount of glucose released from potato starch during tree-stage simulated digestion, with IC₅₀ value equal to 87.77 µg/mL and 148.87 µg/mL, respectively. Phenolic bark extract showed 34.9% and 38.4% more potent inhibitory activity against α-amylase and α-glucosidase, respectively, but the activity of plant extracts was lower than that of acarbose. Chlorogenic acid (27.26% of total phenolics) and (+)-catechin (30.48% of total phenolics) were the most prominent phenolics in the flower and bark extracts, respectively. Procyanidins may be responsible for the strongest V. opulus bark inhibitory activity against α-amylase, while (+)-catechin relative to α-glucosidase. This preliminary study provides the basis of further examination of the suitability of V. opulus bark compounds as components of nutraceuticals and functional foods with antidiabetic activity.     

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

Diabetes mellitus (DM) is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel α-glucosidase and α-amylase inhibitors that are both effective and potentially safe. Traditional methodologies are being replaced with new techniques that are less complicated and less time demanding; yet, both the experimental and computational strategies are viable and complementary in drug discovery and development. As a result, this study was conducted to investigate the in vitro anti-diabetic potential of aqueous acetone Helichrysum petiolare and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-d-glucose uptake assay. In addition, we performed molecular docking of the flavonoid constituents identified and quantified by liquid chromatography-mass spectrometry (LC-MS) from AAHPE with the potential to serve as effective and safe α-amylase and α-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both α-amylase and α-glucosidase, with IC₅₀ values of 46.50 ± 6.17 (µg/mL) and 37.81 ± 5.15 (µg/mL), respectively. This is demonstrated by a significant increase in the glucose uptake activity percentage in a concentration-dependent manner compared to the control, with the highest AAHPE concentration of 75 µg/mL of glucose uptake activity being higher than metformin, a standard anti-diabetic drug, in the insulin-resistant HepG2 cell line. The molecular docking results displayed that the constituents strongly bind α-amylase and α-glucosidase while achieving better binding affinities that ranged from ΔG = −7.2 to −9.6 kcal/mol (compared with acarbose ΔG = −6.1 kcal/mol) for α-amylase, and ΔG = −7.3 to −9.0 kcal/mol (compared with acarbose ΔG = −6.3 kcal/mol) for α-glucosidase. This study revealed the potential use of the H. petiolare plant extract and its phytochemicals, which could be explored to develop potent and safe α-amylase and α-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.     

Carbohydrate Hydrolase-Inhibitory Activity of Juice-Based Phenolic Extracts in Correlation to Their Anthocyanin/Copigment Profile

Red fruits and their juices are rich sources of polyphenols, especially anthocyanins. Some studies have shown that such polyphenols can inhibit enzymes of the carbohydrate metabolism, such as α-amylase and α-glucosidase, that indirectly regulate blood sugar levels. The presented study examined the in vitro inhibitory activity against α-amylase and α-glucosidase of various phenolic extracts prepared from direct juices, concentrates, and purees of nine different berries which differ in their anthocyanin and copigment profile. Generally, the extracts with the highest phenolic content—aronia (67.7 ± 3.2 g GAE/100 g; cyanidin 3-galactoside; chlorogenic acid), pomegranate (65.7 ± 7.9 g GAE/100 g; cyanidin 3,5-diglucoside; punicalin), and red grape (59.6 ± 2.5 g GAE/100 g; malvidin 3-glucoside; quercetin 3-glucuronide)—showed also one of the highest inhibitory activities against α-amylase (326.9 ± 75.8 μg/mL; 789.7 ± 220.9 μg/mL; 646.1 ± 81.8 μg/mL) and α-glucosidase (115.6 ± 32.5 μg/mL; 127.8 ± 20.1 μg/mL; 160.6 ± 68.4 μg/mL) and, partially, were even more potent inhibitors than acarbose (441 ± 30 μg/mL; 1439 ± 85 μg/mL). Additionally, the investigation of single anthocyanins and glycosylated flavonoids demonstrated a structure- and size-dependent inhibitory activity. In the future in vivo studies are envisaged.     

Nutritional Profiling,Phytochemical Composition and Antidiabetic Potential of Taraxacum officinale,an Underutilized Herb

Taraxacum officinale (T. officinale), a wild vegetable with a number of health claims, has been mostly ignored and unexplored. The study aims to compare the nutritional, phytochemical as well as antidiabetic potential of fresh as well as shade-dried leaves of T. officinale, in order to recommend its best form as a dietary antidiabetic product. The results revealed that as compared to fresh leaves, the shade-dried leaves, in addition to possessing higher levels of carbohydrates, crude protein, crude fat, crude fiber, etc., also contain appreciable amounts of total phenols (5833.12 ± 4.222 mg/100), total flavonoids (188.84 ± 0.019 mg/100 g), ascorbic acid (34.70 ± 0.026 mg/100 g), β-carotene (3.88 ± 1.473 mg/100 g) and total chlorophyll (239.51 ± 0.015 mg/100 g) antioxidants. The study revealed the presence of medicinally important antidiabetic flavonoid quercetin present in T. officinale leaves. Among the three solvent systems used, the aqueous extract of shade-dried T. officinale leaves comparatively demonstrated potent antidiabetic activity under in vitro conditions in a dose-dependent manner via targeting α-amylase and α-glucosidase, the two potent enzymes of carbohydrate metabolism. Therefore, in addition to being a nutritious herb, the shade-dried leaves of T. officinale have great potential to suppress post-prandial glucose rise and can be better exploited through clinical trials to be used as a dietary intervention for better management of diabetes.     

UHPLC-DAD Characterization of Origanum vulgare L. from Atacama Desert Andean Region and Antioxidant,Antibacterial and Enzyme Inhibition Activities

The Lamiaceae family is an important source of species among medicinal plants highly valued for their biological properties and numerous uses in folk medicine. Origanum is one of the main genera that belong to this family. The purpose of the study was to determine the phenolic composition of the Origanum vulgare extract and evaluate the antimicrobial, antioxidant, and inhibitory activities of this species that grows in the Andean region of the Atacama Desert. High-performance liquid chromatography was performed to determine the main phenols. Rosmarinic acid was identified as the predominant phenolic compound in this species (76.01 mg/100 g DW), followed by protocatechuic acid, which to our knowledge, no previous study reported similar concentrations in O. vulgare. The oregano extract exhibited a content of total phenolic (3948 mg GAE/100 g DW) and total flavonoid (593 mg QE/100 g DW) with a higher DPPH antioxidant activity (IC₅₀ = 40.58 µg/mL), compared to the same species grown under other conditions. Furthermore, it was found to inhibit α-glucosidase activity with an IC₅₀ value (7.11 mg/mL) lower than acarbose (129.32 mg/mL). Pseudomonas syringae and Pantoea agglomerans (both MIC 0.313 mg/mL and MBC 1.25 mg/mL) were the bacteria most susceptible to oregano extract with the lowest concentration necessary to inhibit bacterial growth. These results open the door for the potential use of this plant to manage chronic diseases, and they expand the knowledge of the species cultivated in arid environmental conditions.     

The Inhibition of α-Glucosidase, α-Amylase and Protein Glycation by Phenolic Extracts of Cotoneaster bullatus,Cotoneaster zabelii,and Cotoneaster integerrimus Leaves and Fruits: Focus on Anti-Hyperglycemic Activity and Kinetic Parameters

Cotoneaster species have gained significant importance in traditional Asian medicine for their ability to prevent and treat hyperglycemia and diabetes. Therefore, in this study, some aspects of the beneficial health effects of hydromethanolic extracts of C. bullatus, C. zabelii, and C. integerrimus leaves and fruits were evaluated, including their influence on α-glucosidase, α-amylase, and nonenzymatic protein glycation. The activity was investigated in relation to the polyphenolic profile of the extracts determined by UV-spectrophotometric and HPLC-PDA-fingerprint methods. It was revealed that all leaf and fruit extracts are a promising source of biological components (caffeic acid pseudodepsides, proanthocyanidins, and flavonols), and the leaf extracts of C. bullatus and C. zabelii contain the highest levels of polyphenols (316.3 and 337.6 mg/g in total, respectively). The leaf extracts were also the most effective inhibitors of digestive enzymes and nonenzymatic protein glycation. IC₅₀ values of 8.6, 41.8, and 32.6 µg/mL were obtained for the most active leaf extract of C. bullatus (MBL) in the α-glucosidase, α-amylase, and glycation inhibition tests, respectively. In the kinetic study, MBL was displayed as a mixed-type inhibitor of both enzymes. The correlations between the polyphenol profiles and activity parameters (|r| > 0.72, p < 0.05) indicate a significant contribution of proanthocyanidins to the tested activity. These results support the traditional use of Cotoneaster leaves and fruits in diabetes and suggest their hydrophilic extracts be promising in functional applications.     

Synthesis and Characterization of Andrographolide Derivatives as Regulators of βAPP Processing in Human Cells

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5′,7′-dichloro-8′-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2′-methyl-5′,7′-dichloro-8′-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as β-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting β-secretase that could prove useful in our quest for the therapeutic treatment of AD.     

Chemical Diversity of Essential Oil of Valeriana jatamansi from Different Altitudes of Himalaya and Distillation Methods

Valeriana jatamansi is an important temperate herb that is used in the pharmaceutical and essential oil industries. In India, this species is now on the verge of extinction due to the over-exploitation of its rhizomes from its natural habitat. It is hypothesized that the variations in bioactive compounds in its essential oil are very high among the wild populations as well as cultivated sources. Thus, this study was conducted to evaluate the chemical profiling of essential oil of four wild populations (Rupena, Kugti, Garola, and Khani) and two cultivated sources (CSIR-IHBT, Salooni), which were distilled at three consecutive days. The variation in oil concentration in roots/rhizomes was found significant (p ≤ 0.05), and the maximum value (0.35%) was registered with the population collected from Kugti and Khani. In essential oil, irrespective of population and distillation day, patchouli alcohol was the major compound, which ranged from 19 to 63.1%. The maximum value (63.1%) was recorded with the essential oil obtained from Garola’s population and distilled on the first day. The percentage of seychellene was abruptly increased with subsequent days of extraction in all the populations. The multivariate analysis revealed that the essential oil profiles of Rupena, Kugti, Garola, and CSIR-IHBT populations were found to be similar during the first day of distillation. However, during the second day, Rupena, Kugti, Khani, and CSIR-IHBT came under the same ellipse of 0.95% coefficient. The results suggest that the population of Kugti is superior in terms of oil concentration (0.35%), with a higher proportion of patchouli alcohol (63% on the first day). Thus, repeated distillation is recommended for higher recovery of essential oil. Moreover, repeated distillation can be used to attain V. jatamansi essential oil with differential and perhaps targeted definite chemical profile.     

In Vitro Evaluation of α-amylase and α-glucosidase Inhibition of 2,3-Epoxyprocyanidin C1 and Other Constituents from Pterocarpus erinaceus Poir

Diabetes mellitus is a metabolic disorder which is one of the leading causes of mortality and morbidities in elderly humans. Chronic diabetes can lead to kidney failure, blindness, limb amputation, heart attack and stroke. Physical activity, healthy diets and medications can reduce the incidence of diabetes, so the search for more efficient antidiabetic therapies, most especially from natural products, is a necessity. Herein, extract from roots of the medicinal plant Pterocarpus erinaceus was purified by column chromatography and afforded ten compounds which were characterized by EIMS, HR-FAB-MS, 1D and 2D NMR techniques. Amongst them were, a new trimeric derivative of epicatechin, named 2,3-Epoxyprocyanidin C1 (1); two pentacyclic triterpenoids, friedelin (2) and betulin (3); angolensin (4); flavonoids such as 7-methoxygenistein (5), 7-methoxydaidzein (6), apigenin 7-O-glucoronide (8) and naringenin 7-O-β-D-glucopyranoside (9); and an ellagic acid derivative (10). The extract and compounds were evaluated for their antidiabetic potential by α-amylase and α-glucosidase inhibitory assays. IC₅₀ values of compound 7 (48.1 ± 0.9 µg/mL), compound 8 (48.6 ± 0.1 µg/mL), compound 9 (50.2 ± 0.5 µg/mL) and extract (40.5 ± 0.8 µg/mL) when compared to that of acarbose (26.4 ± 0.3 µg/mL) indicated good α-amylase inhibition. In the α-glucosidase assay, the extract (IC₅₀ = 31.2 ± 0.1 µg/mL), compound 7 (IC₅₀ = 39.5 ± 1.2 µg/mL), compound 8 (IC₅₀ = 40.9 ± 1.3 µg/mL), compound 1 (IC₅₀ = 41.6 ± 1.0 µg/mL), Compound 4 (IC₅₀ = 43.4 ± 0.5 µg/mL), compound 5 (IC₅₀ = 47.6 ± 0.9 µg/mL), compound 6 (IC₅₀ = 46.3 ± 0.2 µg/mL), compound 7 (IC₅₀ = 45.0 ± 0.8 µg/mL), compound 9 (IC₅₀ = 44.8 ± 0.6 µg/mL) and compound 11 (IC₅₀ = 47.5 ± 0.4 µg/mL) all had moderate-to-good inhibitions, compared to acarbose (IC₅₀ = 22.0 ± 0.5 µg/mL). The ability to inhibit α-amylase and α-glucosidase indicates that P. erinaceus and its compounds can lower blood glucose levels by delaying hydrolysis of carbohydrates into sugars, thereby providing a source of natural antidiabetic remedy.     

Synthesis and Biological Evaluation of Harmirins,Novel Harmine–Coumarin Hybrids as Potential Anticancer Agents

As cancer remains one of the major health burdens worldwide, novel agents, due to the development of resistance, are needed. In this work, we designed and synthesized harmirins, which are hybrid compounds comprising harmine and coumarin scaffolds, evaluated their antiproliferative activity, and conducted cell localization and cell cycle analysis experiments. Harmirins were prepared from the corresponding alkynes and azides under mild reaction conditions using Cu(I) catalyzed azide–alkyne cycloaddition, leading to the formation of the 1H-1,2,3-triazole ring. Antiproliferative activity of harmirins was evaluated in vitro against four human cancer cell lines (MCF-7, HCT116, SW620, and HepG2) and one human non-cancer cell line (HEK293T). The most pronounced activities were exerted against MCF-7 and HCT116 cell lines (IC₅₀ in the single-digit micromolar range), while the most selective harmirins were 5b and 12b, substituted at C-3 and O-7 of the β-carboline core and bearing methyl substituent at position 6 of the coumarin ring (SIs > 7.2). Further experiments demonstrated that harmirin 12b is localized exclusively in the cytoplasm. In addition, it induced a strong G1 arrest and reduced the percentage of cells in the S phase, suggesting that it might exert its antiproliferative activity through inhibition of DNA synthesis, rather than DNA damage. In conclusion, harmirin 12b is a novel harmine and coumarin hybrid with significant antiproliferative activity and warrants further evaluation as a potential anticancer agent.     

Insight into Gentisic Acid Antidiabetic Potential Using In Vitro and In Silico Approaches

Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the antidiabetic potential of gentisic acid and highlight its mechanisms of action following in silico and in vitro approaches. The in silico study was intended to predict the interaction of GA with eight different receptors highly involved in the management and complications of diabetes (dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), α-amylase, peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase), while the in vitro study studied the potential inhibitory effect of GA against α-amylase and α-glucosidase. The results indicate that GA interacted moderately with most of the receptors and had a moderate inhibitory activity during the in vitro tests. The study therefore encourages further in vivo studies to confirm the given results.