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Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioorganic Chemistry and Medicinal Chemistry".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 7013

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Dr. Hidayat Hussain

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Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Interests: natural product; chemistry; medicinal chemistry; cancer biology; bioorganic chemistry; pharmacology; diabetes; synthetic chemistry; biology oriented synthesis
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Dear Colleagues,

Natural products (NPs) have played a crucial role in the drug discovery process in order to treat numerous diseases. Plants, fungi, bacteria, and other natural sources produce NPs with intriguing chemical diversity illustrating interesting biological effects for numerous disease treatments. Notably, NP-based drugs are usually considered to be safer, cheaper, and easily available. Diabetes is one of the chronic disorders associated with high mortality risk. Unfortunately, the currently used drugs have been identified with one or more adverse effects. This indicates that there is still an urgent need for the development of novel antidiabetic drugs with a unique mechanism of action.

The focus of this Special Issue is on natural products (NPs)-based antidiabetic molecules and NPs-based synthetic antidiabetic compounds. Furthermore, this Issue will also place emphasis on the relationship between the chemical structure and the biological activity of the molecules at the molecular level together with applying bioinformatics in diabetes. Moreover, this Special Issue also welcomes articles on the antidiabetic effects of α-glucosidase, amylase, protein tyrosine phosphatase 1B (PTP1B), and dipeptidyl peptidase (DPP)-4 inhibition at the molecular level (kinetic studies). This Special Issue will also focus on the development of new therapeutic agents for diabetes treatment, employing the newest techniques of pharmacology, biotechnology, and genetic engineering. This Issue welcomes original articles, communications, and reviews dealing with diabetes treatment.

Dr. Hidayat Hussain
Guest Editor

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Keywords

natural products
natural product derivatives
antidiabetic agents
α-glucosidase inhibitors
amylase inhibitors
PTP1B inhibitors
DPP-4 inhibitors
molecular level
kinetic studies
in vitro studies
in vivo studies
computational methods
mode of action

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Published Papers (4 papers)

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Research

14 pages, 1562 KiB

Open AccessArticle

GC-MS Profiling of Ethanol-Extracted Polyherbal Compounds from Medicinal Plant (Citrullus colocynthis, Curcuma longa, and Myristica fragrans): In Silico and Analytical Insights into Diabetic Neuropathy Therapy via Targeting the Aldose Reductase

by Mohd Adnan Kausar, Sadaf Anwar, Halima Mustafa Elagib, Kehkashan Parveen, Malik Asif Hussain, Mohammad Zeeshan Najm, Abhinav Nair and Subhabrata Kar

Curr. Issues Mol. Biol. 2025, 47(2), 75; https://doi.org/10.3390/cimb47020075 - 23 Jan 2025

Viewed by 1114

Abstract

Diabetic neuropathy is one of the severe complications of diabetes, which affects the quality of life in a patient and increases the risk of amputations and chronic wounds. Current therapeutic approaches are symptomatically oriented, focusing on comfort and non-inflammatory aspects without addressing the mechanism or molecular target of the disease. The present study investigates the therapeutic effects of an ethanolic polyherbal extract from Citrullus colocynthis (Bitter Apple), Curcuma longa (Turmeric), and Myristica fragrans (Nutmeg) using advanced in silico and analytical methods. According to the findings, PHE showed the presence of a total of 39 bioactive compounds in GC–MS analysis, which include alcohols, fatty acids, terpenoids, esters, neolignans, phenylpropanoids, and steroids. Three of the compounds—-4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (−11.4 kcal/mol), (1S,2R)-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)-1-propanol (−9.8 kcal/mol) and (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene (−10.3 kcal/mol)—followed the Lipinski rule and showed the binding affinity with aldol reductase. Docking experiments showed that compound 4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (−11.4 kcal/mol) has high-affinity binding to aldose reductase, an enzyme involved in diabetic neuropathy pathophysiology, whereas molecular dynamics simulations show long-range persistence of the interaction of (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene with aldol reductase in physiological conditions. Therefore, this combination of herbal therapy and advanced computational/analytical techniques could be leading towards innovative, multi-targeted therapies against diabetic neuropathy. Nevertheless, further studies in vivo are required to confirm the efficacy, safety, and pharmacokinetics of the PHE in biological systems. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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12 pages, 3771 KiB

Open AccessArticle

The Effect of Geranylgeraniol and Ginger on Satellite Cells Myogenic State in Type 2 Diabetic Rats

by Nigel C. Jiwan, Casey R. Appell, Raoul Sterling, Chwan-Li Shen and Hui-Ying Luk

Curr. Issues Mol. Biol. 2024, 46(11), 12299-12310; https://doi.org/10.3390/cimb46110730 - 31 Oct 2024

Viewed by 1268

Abstract

Type 2 diabetes (T2D) is associated with increased inflammation and reactive oxygen species (ROS) in muscles, leading to basal satellite cell (SC) myogenic impairment (i.e., reduction in SC pool), which is critical for maintaining skeletal muscle mass. T2D may contribute to muscle atrophy, possibly due to reductions in the SC pool. Geranylgeraniol (GGOH) and ginger can reduce inflammation and enhance SC myogenesis in damaged muscles, thereby alleviating muscle atrophy; however, their effect on basal SC myogenic state and muscle mass in T2D rats is limited. Rats consumed a control diet (CON), high-fat diet with 35 mg/kg of streptozotocin (HFD), a HFD with 800 mg/kg body weight of GGOH (GG), or a HFD with 0.75% ginger root extract (GRE). In the eighth week, their soleus muscles were analyzed for Pax7, MyoD, and MSTN gene and protein expression, SC myogenic state, and muscle cross-sectional area (CSA). The HFD group had a significantly lower number of Pax7⁺/MyoD⁻ and Pax7⁺/MSTN⁺ cells, less Pax7 and MyoD gene expression, and less MyoD and MSTN protein expression, with a smaller CSA than the CON group. Compared to the GG and GRE groups, the HFD group had a significantly lower number of Pax7⁺/MSTN⁺ cells, less MyoD protein expression, and smaller CSA. The GRE group also had a significantly lower number of Pax7⁻/MyoD⁺ and greater MSTN protein expression than the HFD group. Nevertheless, the CON group had a significantly greater number of Pax7⁺/MyoD⁻ than the GG and GRE groups, and a greater number of Pax7⁻/MyoD⁺ cells than the GRE group with a larger CSA than the GG group. GGOH and ginger persevered muscle CSA, possibly through increased MyoD and the ability to maintain the SC pool in T2D rats. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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30 pages, 3282 KiB

Open AccessArticle

Influence of Harvesting Stage on Phytochemical Composition, Antioxidant, and Antidiabetic Activity of Immature Ceratonia siliqua L. Pulp from Béni Mellal-Khénifra Region, Morocco: In Silico, In Vitro, and In Vivo Approaches

by Salah Laaraj, Hanane Choubbane, Amal Elrherabi, Aziz Tikent, Ayoub Farihi, Meriem Laaroussi, Mohamed Bouhrim, Abdelaaty A. Shahat, Younes Noutfia, Rashed N. Herqash, Fatiha Chigr, Souad Salmaoui and Kaoutar Elfazazi

Curr. Issues Mol. Biol. 2024, 46(10), 10991-11020; https://doi.org/10.3390/cimb46100653 - 29 Sep 2024

Cited by 4 | Viewed by 1676

Abstract

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with high contents of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Béni Mellal-Khénifra region. The results revealed a gradual increase in total sugar content over the pulp’s ripening period, reaching a value of 2134 ± 56.23 mg GE/100 g fresh weight (FW) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW had the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrated that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibited a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC₅₀ = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC₅₀ = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibited high intestinal absorption. Furthermore, the majority of these compounds did not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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20 pages, 24461 KiB

Open AccessArticle

An Examination of the Effects of Propolis and Quercetin in a Rat Model of Streptozotocin-Induced Diabetic Peripheral Neuropathy

by Sibel Türedi, Hakim Çelik, Şeyda Nur Dağlı, Seyhan Taşkın, Uğur Şeker and Mustafa Deniz

Curr. Issues Mol. Biol. 2024, 46(3), 1955-1974; https://doi.org/10.3390/cimb46030128 - 2 Mar 2024

Cited by 2 | Viewed by 2392

Abstract

The purpose of this study was to reveal the combined effects of propolis (P) and quercetin (Q) against diabetic peripheral neuropathy developing with streptozotocin-induced diabetes in rats. Sixty-four adult male rats were divided into eight equal groups: control, P (100 mg/kg/day), Q (100 mg/kg/day), P + Q (100 mg/day for both), diabetes mellitus (DM) (single-dose 60 mg/kg streptozotocin), DM + P, DM + Q, and DM + P + Q. The rats were sacrificed, and blood and sciatic nerve tissues were collected. Blood glucose and malondialdehyde (MDA) levels increased, while IL-6 and total antioxidant status decreased in the DM group (p = 0.016 and p = 0.047, respectively). Ultrastructural findings showed degeneration of the axon and myelin sheath. The apoptotic index (AI %), TNF-α, and IL-1β immunopositivity increased significantly in the DM group (p < 0.001). Morphological structures approaching those of the controls were observed in the DM + P, DM + Q, and DM + P + Q groups. Morphometric measurements increased markedly in all treatment groups (p < 0.001), while blood glucose and MDA levels, AI (%), TNF-α, and IL-1β immunopositivity decreased. In conclusion, the combined effects of propolis and quercetin in diabetic neuropathy may provide optimal morphological protection with neuroprotective effects by reducing hyperglycemia, and these may represent a key alternative supplement in regenerative medicine. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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