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18 pages, 2532 KiB

Open AccessArticle

Multitarget Action of Xanthones from Garcinia mangostana against α-Amylase, α-Glucosidase and Pancreatic Lipase

by Juan Cardozo-Muñoz, Luis E. Cuca-Suárez, Juliet A. Prieto-Rodríguez, Fabian Lopez-Vallejo and Oscar J. Patiño-Ladino

Molecules 2022, 27(10), 3283; https://doi.org/10.3390/molecules27103283 - 20 May 2022

Cited by 11 | Viewed by 2115

Abstract

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there [...] Read more.

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1–5). Six derivatives (6–11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC₅₀ values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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24 pages, 5808 KiB

Open AccessArticle

Ameliorative Effect of Ocimum forskolei Benth on Diabetic, Apoptotic, and Adipogenic Biomarkers of Diabetic Rats and 3T3-L1 Fibroblasts Assisted by In Silico Approach

by Hany Ezzat Khalil, Miada F. Abdelwahab, Promise Madu Emeka, Lorina I. Badger-Emeka, Krishnaraj Thirugnanasambantham, Hairul-Islam Mohamed Ibrahim, Sara Mohamed Naguib, Katsuyoshi Matsunami and Nada M. Abdel-Wahab

Molecules 2022, 27(9), 2800; https://doi.org/10.3390/molecules27092800 - 28 Apr 2022

Cited by 9 | Viewed by 2429

Abstract

Diabetes mellitus (DM) is a complicated condition that is accompanied by a plethora of metabolic symptoms, including disturbed serum glucose and lipid profiles. Several herbs are reputed as traditional medicine to improve DM. The current study was designed to explore the chemical composition [...] Read more.

Diabetes mellitus (DM) is a complicated condition that is accompanied by a plethora of metabolic symptoms, including disturbed serum glucose and lipid profiles. Several herbs are reputed as traditional medicine to improve DM. The current study was designed to explore the chemical composition and possible ameliorative effects of Ocimum forskolei on blood glucose and lipid profile in high-fat diet/streptozotocin-induced diabetic rats and in 3T3-L1 cell lines as a first report of its bioactivity. Histopathological study of pancreatic and adipose tissues was performed in control and treatment groups, along with quantification of glucose and lipid profiles and the assessment of NF-κB, cleaved caspase-3, BAX, and BCL2 markers in rat pancreatic tissue. Glucose uptake, adipogenic markers, DGAT1, CEBP/α, and PPARγ levels were evaluated in the 3T3-L1 cell line. Hesperidin was isolated from total methanol extract (TME). TME and hesperidin significantly controlled the glucose and lipid profile in DM rats. Glibenclamide was used as a positive control. Histopathological assessment showed that TME and hesperidin averted necrosis and infiltration in pancreatic tissues, and led to a substantial improvement in the cellular structure of adipose tissue. TME and hesperidin distinctly diminished the mRNA and protein expression of NF-κB, cleaved caspase-3, and BAX, and increased BCL2 expression (reflecting its protective and antiapoptotic actions). Interestingly, TME and hesperidin reduced glucose uptake and oxidative lipid accumulation in the 3T3-L1 cell line. TME and hesperidin reduced DGAT1, CEBP/α, and PPARγ mRNA and protein expression in 3T3-L1 cells. Moreover, docking studies supported the results via deep interaction of hesperidin with the tested biomarkers. Taken together, the current study demonstrates Ocimum forskolei and hesperidin as possible candidates for treating diabetes mellitus. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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24 pages, 2743 KiB

Open AccessArticle

Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study

by Md Yousof Ali, Sumera Zaib, Susoma Jannat, Imtiaz Khan, M. Mizanur Rahman, Seong Kyu Park and Mun Seog Chang

Molecules 2022, 27(7), 2134; https://doi.org/10.3390/molecules27072134 - 25 Mar 2022

Cited by 9 | Viewed by 2296

Abstract

This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using _DL-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20S) [...] Read more.

This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using _DL-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20S) ginsenoside Rg3, (20R) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC₅₀ values of 0.67, 1.25, 4.28, and 7.28 µM, respectively. Moreover, protopanaxadiol, protopanaxatriol, compound K, and ginsenoside Rh1 were potent inhibitors of HRAR, with IC₅₀ values of 0.36, 1.43, 2.23, and 4.66 µM, respectively. The relationship of structure–activity exposed that the existence of hydroxyl groups, linkages, and their stereo-structure, as well as the sugar moieties of the ginsenoside skeleton, represented a significant role in the inhibition of HRAR and RLAR. Additional, various modes of ginsenoside inhibition and molecular docking simulation indicated negative binding energies. It was also indicated that it has a strong capacity and high affinity to bind the active sites of enzymes. Further, active ginsenosides suppressed sorbitol accumulation in rat lenses under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. The findings of the present study suggest the potential of ginsenoside derivatives for use in the development of therapeutic or preventive agents for diabetic complications. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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11 pages, 678 KiB

Open AccessArticle

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

by Elham Amin, Mohamed Sadek Abdel-Bakky, Mostafa Assem Darwish, Hamdoon A. Mohammed, Sridevi Chigurupati, Kamal Ahmad Qureshi and Marwa H. A. Hassan

Molecules 2022, 27(3), 973; https://doi.org/10.3390/molecules27030973 - 01 Feb 2022

Cited by 10 | Viewed by 2008

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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16 pages, 3643 KiB

Open AccessArticle

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications

by Hesham El-Askary, Heba H. Salem and Amira Abdel Motaal

Molecules 2022, 27(3), 857; https://doi.org/10.3390/molecules27030857 - 27 Jan 2022

Cited by 12 | Viewed by 2924

Abstract

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the [...] Read more.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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17 pages, 1837 KiB

Open AccessArticle

Anti-Obesity Effects of Matoa (Pometia pinnata) Fruit Peel Powder in High-Fat Diet-Fed Rats

by Toshikazu Suzuki, Mayumi Nagata, Natsuko Kagawa, Shiori Takano, Nahrowi and Jun Nomura

Molecules 2021, 26(21), 6733; https://doi.org/10.3390/molecules26216733 - 07 Nov 2021

Cited by 7 | Viewed by 2888

Abstract

Fruit peels, pericarps, or rinds are rich in phenolic/polyphenolic compounds with antioxidant properties and potentially beneficial effects against obesity and obesity-related non-communicable diseases. This study investigated the anti-obesity effects of matoa (Pometia pinnata) and salak (Salacca zalacca) fruit peel. [...] Read more.

Fruit peels, pericarps, or rinds are rich in phenolic/polyphenolic compounds with antioxidant properties and potentially beneficial effects against obesity and obesity-related non-communicable diseases. This study investigated the anti-obesity effects of matoa (Pometia pinnata) and salak (Salacca zalacca) fruit peel. Neither matoa peel powder (MPP) nor salak peel powder (SPP) affected the body weight, visceral fat weight, or serum glucose or lipid levels of Sprague–Dawley rats when included as 1% (w/w) of a high-fat diet (HFD). However, MPP significantly decreased the hepatic lipid level. MPP at a dose of 3% (w/w) of the HFD decreased body weight, visceral fat, and serum triglyceride levels as well as the hepatic lipid content. The inhibitory effect of MPP on hepatic lipid accumulation was not enhanced when its concentration was increased from 1% to 3% of the HFD. The anti-obesity effect of matoa was partly explained by the inhibitory effect of the matoa peel extract on fatty acid-induced secretion of ApoB-48 protein, a marker of intestinal chylomicrons, in differentiated Caco-2 cell monolayers. We identified hederagenin saponins that are abundant in MPP as potential anti-obesity substances. These results will contribute towards the development of functional foods with anti-obesity effects using the matoa fruit peel. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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14 pages, 2914 KiB

Open AccessArticle

Identification of Insulin-Mimetic Plant Extracts: From an In Vitro High-Content Screen to Blood Glucose Reduction in Live Animals

by Verena Stadlbauer, Cathrina Neuhauser, Tobias Aumiller, Alexander Stallinger, Marcus Iken and Julian Weghuber

Molecules 2021, 26(14), 4346; https://doi.org/10.3390/molecules26144346 - 18 Jul 2021

Cited by 8 | Viewed by 2554

Abstract

Type 2 diabetes mellitus (T2DM) is linked to insulin resistance and a loss of insulin sensitivity, leading to millions of deaths worldwide each year. T2DM is caused by reduced uptake of glucose facilitated by glucose transporter 4 (GLUT4) in muscle and adipose tissue [...] Read more.

Type 2 diabetes mellitus (T2DM) is linked to insulin resistance and a loss of insulin sensitivity, leading to millions of deaths worldwide each year. T2DM is caused by reduced uptake of glucose facilitated by glucose transporter 4 (GLUT4) in muscle and adipose tissue due to decreased intracellular translocation of GLUT4-containing vesicles to the plasma membrane. To treat T2DM, novel medications are required. Through a fluorescence microscopy-based high-content screen, we tested more than 600 plant extracts for their potential to induce GLUT4 translocation in the absence of insulin. The primary screen in CHO-K1 cells resulted in 30 positive hits, which were further investigated in HeLa and 3T3-L1 cells. In addition, full plasma membrane insertion was examined by immunostaining of the first extracellular loop of GLUT4. The application of appropriate inhibitors identified PI3 kinase as the most important signal transduction target relevant for GLUT4 translocation. Finally, from the most effective hits in vitro, four extracts effectively reduced blood glucose levels in chicken embryos (in ovo), indicating their applicability as antidiabetic pharmaceuticals or nutraceuticals. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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14 pages, 3169 KiB

Open AccessArticle

Methanolic Extract of Piper sarmentosum Attenuates Obesity and Hyperlipidemia in Fructose-Induced Metabolic Syndrome Rats

by Sivanesan Raja Kumar, Elvy Suhana Mohd Ramli, Nurul Alimah Abdul Nasir, Nafeeza Mohd Ismail and Nur Azlina Mohd Fahami

Molecules 2021, 26(13), 3985; https://doi.org/10.3390/molecules26133985 - 29 Jun 2021

Cited by 4 | Viewed by 2904

Abstract

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This [...] Read more.

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG—Untreated group; CTRL—control; FDW—olive oil + 20% fructose; FDW-PS—PS (125 mg/kg) + 20% fructose; FDW-NGN—naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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13 pages, 15816 KiB

Open AccessArticle

Thymoquinone Lowers Blood Glucose and Reduces Oxidative Stress in a Rat Model of Diabetes

by Mohamed Faisal Lutfi, Abdel-Moneim Hafez Abdel-Moneim, Ashwag Saleh Alsharidah, Mugahid A. Mobark, Ahmed A. H. Abdellatif, Imran Y. Saleem, Osamah Al Rugaie, Khalid M. Mohany and Mansour Alsharidah

Molecules 2021, 26(8), 2348; https://doi.org/10.3390/molecules26082348 - 17 Apr 2021

Cited by 16 | Viewed by 2866

Abstract

The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group [...] Read more.

The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group I received no medication (control). The rats in groups I and II were then given distilled water, while the rats in group III were given TQ at a dose of 50 mg/kg body weight/day for 4 weeks. Lipid peroxidase, nitric oxide (NO), total antioxidant capacity (TAC), glycated haemoglobin (HbA1c), lipid profiles, and renal function were assessed. Moreover, the renal tissues were used for histopathological examination. STZ increased the levels of HbA1c, lipid peroxidase, NO, and creatinine in STZ-induced diabetic rats in comparison to control rats. TAC was lower in STZ-induced diabetic rats than in the control group. Furthermore, rats treated with TQ exhibited significantly lower levels of HbA1c, lipid peroxidase, and NO than did untreated diabetic rats. TAC was higher in diabetic rats treated with TQ than in untreated diabetic rats. The histopathological results showed that treatment with TQ greatly attenuated the effect of STZ-induced diabetic nephropathy. TQ effectively adjusts glycaemic control and reduces oxidative stress in STZ-induced diabetic rats without significant damaging effects on the renal function. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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11 pages, 2221 KiB

Open AccessArticle

Assessing the In Vitro Inhibitory Effects on Key Enzymes Linked to Type-2 Diabetes and Obesity and Protein Glycation by Phenolic Compounds of Lauraceae Plant Species Endemic to the Laurisilva Forest

by Vítor Spínola and Paula C. Castilho

Molecules 2021, 26(7), 2023; https://doi.org/10.3390/molecules26072023 - 01 Apr 2021

Cited by 6 | Viewed by 2482

Abstract

Methanolic leaf extracts of four Lauraceae species endemic to Laurisilva forest (Apollonias barbujana, Laurus novocanariensis, Ocotea foetens and Persea indica) were investigated for the first time for their potential to inhibit key enzymes linked to type-2 diabetes (α-amylase, α-glucosidase, [...] Read more.

Methanolic leaf extracts of four Lauraceae species endemic to Laurisilva forest (Apollonias barbujana, Laurus novocanariensis, Ocotea foetens and Persea indica) were investigated for the first time for their potential to inhibit key enzymes linked to type-2 diabetes (α-amylase, α-glucosidase, aldose reductase) and obesity (pancreatic lipase), and protein glycation. Lauraceae extracts revealed significant inhibitory activities in all assays, altough with different ability between species. In general, P. indica showed the most promissing results. In the protein glycation assay, all analysed extracts displayed a stronger effect than a reference compound: aminoguanidine (AMG). The in vitro anti-diabetic, anti-obesity and anti-glycation activities of analysed extracts showed correlation with their flavonols and flavan-3-ols (in particular, proanthocyanins) contents. These Lauraceae species have the capacity to assist in adjuvant therapy of type-2 diabetes and associated complications, through modulation of the activity of key metabolic enzymes and prevention of advanced glycation end-products (AGEs) formation. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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22 pages, 7701 KiB

Open AccessArticle

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action

by Mohamed Bouhrim, Hayat Ouassou, Salima Boutahiri, Nour Elhouda Daoudi, Hamza Mechchate, Bernard Gressier, Bruno Eto, Hamada Imtara, Amal A. Alotaibi, Mohammed Al-zharani, Abderrahim Ziyyat, Hassane Mekhfi, Abdelkhaleq Legssyer, Mohammed Aziz and Mohamed Bnouham

Molecules 2021, 26(6), 1677; https://doi.org/10.3390/molecules26061677 - 17 Mar 2021

Cited by 19 | Viewed by 3219

Abstract

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic [...] Read more.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC₅₀ = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC₅₀ = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC₅₀ = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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18 pages, 2721 KiB

Open AccessArticle

Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis

by Lena Seidemann, Anne Krüger, Victoria Kegel-Hübner, Daniel Seehofer and Georg Damm

Molecules 2021, 26(4), 1156; https://doi.org/10.3390/molecules26041156 - 22 Feb 2021

Cited by 15 | Viewed by 2487

Abstract

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPARα were abolished by high hepatic lipid levels. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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10 pages, 1901 KiB

Open AccessArticle

Antiobesity Activity of Elateriospermum tapos Shell Extract in Obesity-Induced Sprague Dawley Rats

by Kokila Vani Perumal, Nor Liyana Ja’afar, Che Norma Mat Taib, Nurul Husna Shafie and Hasnah Bahari

Molecules 2021, 26(2), 321; https://doi.org/10.3390/molecules26020321 - 09 Jan 2021

Cited by 8 | Viewed by 2631

Abstract

Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. Orlistat is currently available to treat obesity, but it is associated with adverse side effects. Natural resources are widely used for obesity treatment. Hence, this [...] Read more.

Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. Orlistat is currently available to treat obesity, but it is associated with adverse side effects. Natural resources are widely used for obesity treatment. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. A hot aqueous method for the extraction of E. tapos shells was applied by using 500 mL of distilled water for about 24 h. Various dosages of E. tapos shell extract (10 mg/kg, 100 mg/kg, and 200 mg/kg) were used. At the end of the study, body weight, caloric intake, organ weight, lipid profile, lipoprotein lipase (LPL) activity, and histopathology analysis were carried out. E. tapos shell extract treated groups showed a reduction in body weight, positive lipid-lowering effect, decrements in triglyceride accumulation and LPL activity, and positive improvement in histopathology analysis. A dose of 200 mg/kg showed the most effective result compared to 10 mg/kg and 100 mg/kg doses. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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10 pages, 1819 KiB

Open AccessArticle

In Vitro Alpha-Amylase and Alpha-Glucosidase Inhibitory Activity and In Vivo Antidiabetic Activity of Withania frutescens L. Foliar Extract

by Hamza Mechchate, Imane Es-safi, Abdelhadi Louba, Ali S. Alqahtani, Fahd A. Nasr, Omar M. Noman, Muhammad Farooq, Mohammed S. Alharbi, Abdulaziz Alqahtani, Amina Bari, Hicham Bekkari and Dalila Bousta

Molecules 2021, 26(2), 293; https://doi.org/10.3390/molecules26020293 - 08 Jan 2021

Cited by 56 | Viewed by 8750

Abstract

Withania frutescens L. is a wild perennial woody plant used by the local population for diverse therapeutic purposes. This work aims to study for the first time the potential inhibitory effect of this plant hydroethanolic extract on α-amylase and α-glucosidase activities using in [...] Read more.

Withania frutescens L. is a wild perennial woody plant used by the local population for diverse therapeutic purposes. This work aims to study for the first time the potential inhibitory effect of this plant hydroethanolic extract on α-amylase and α-glucosidase activities using in vitro methods and its antidiabetic and antihyperglycemic activities using alloxan-induced diabetic mice as a model for experimental diabetes. Two doses were selected for the in vivo study (200 and 400 mg/kg) and glibenclamide, a well-known antidiabetic drug (positive control) in a subacute study (28 days) where the antihyperglycemic activity was also assessed over a period of 12 h on diabetic mice. The continuous treatment of diabetic mice with the extract of Withania frutescens for 4 weeks succeeded to slowly manage their high fasting blood glucose levels (after two weeks), while the antihyperglycemic test result revealed that the extract of this plant did not control hyperglycemia in the short term. No toxicity signs or death were noted for the groups treated with the plant extract, and it shows a protective effect on the liver and kidney. The in vitro assays demonstrated that the inhibition of alpha-amylase and alpha-glucosidase might be one of the mechanisms of action exhibited by the extract of this plant to control and prevent postprandial hyperglycemia. This work indicates that W. frutescens have an important long term antidiabetic effect that can be well established to treat diabetes. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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16 pages, 3653 KiB

Open AccessArticle

Novel Function of α-Cubebenoate Derived from Schisandra chinensis as Lipogenesis Inhibitor, Lipolysis Stimulator and Inflammasome Suppressor

by Su Ji Bae, Ji Eun Kim, Yun Ju Choi, Su Jin Lee, Jeong Eun Gong, Young-Whan Choi and Dae Youn Hwang

Molecules 2020, 25(21), 4995; https://doi.org/10.3390/molecules25214995 - 28 Oct 2020

Cited by 14 | Viewed by 2330

Abstract

The efficacy of α-cubebenoate isolated from Schisandra chinensis has been previously studied in three disease areas, namely inflammation, sepsis, and allergy, and its role in other diseases is still being explored. To identify the novel function of α-cubebenoate on lipid metabolism and related [...] Read more.

The efficacy of α-cubebenoate isolated from Schisandra chinensis has been previously studied in three disease areas, namely inflammation, sepsis, and allergy, and its role in other diseases is still being explored. To identify the novel function of α-cubebenoate on lipid metabolism and related inflammatory response, alterations in fat accumulation, lipogenesis, lipolysis, and inflammasome activation were measured in 3T3-L1 preadipocytes and primary adipocytes treated with α-cubebenoate. Lipid accumulation significantly decreased in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with α-cubebenoate without any significant cytotoxicity. The mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT-enhancer binding protein (C/EBP) α for adipogenesis, as well as adipocyte fatty acid binding protein 2 (aP2) and fatty acid synthetase (FAS) for lipogenesis, were reduced after α-cubebenoate treatment, while cell cycle arrest at G2/M stage was restored in the same group. α-cubebenoate treatment induced glycerol release in primary adipocytes and enhanced expression of lipolytic proteins (HSL, perilipin, and ATGL) expression in MDI-stimulated 3T3-L1 adipocytes. Inflammasome activation and downstream cytokines expression were suppressed with α-cubebenoate treatment, but the expression of insulin receptor signaling factors was remarkably increased by α-cubebenoate treatment in MDI-stimulated 3T3-L1 adipocytes. These results indicate that α-cubebenoate may play a novel role as lipogenesis inhibitor, lipolysis stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes. Our results provide the possibility that α-cubebenoate can be considered as one of the candidates for obesity management. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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11 pages, 1821 KiB

Open AccessArticle

Alpha-Glucosidase Inhibitory Effect of Psychotria malayana Jack Leaf: A Rapid Analysis Using Infrared Fingerprinting

by Tanzina Sharmin Nipun, Alfi Khatib, Qamar Uddin Ahmed, Irna Elina Redzwan, Zalikha Ibrahim, Al’aina Yuhainis Firus Khan, Riesta Primaharinastiti, Shaden A. M. Khalifa and Hesham R. El-Seedi

Molecules 2020, 25(18), 4161; https://doi.org/10.3390/molecules25184161 - 11 Sep 2020

Cited by 6 | Viewed by 2552

Abstract

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as “meroyan sakat/salung”. A rapid analytical technique to facilitate the evaluation of the P. malayana leaves’ quality has not been well-established yet. This work aimed therefore to develop [...] Read more.

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as “meroyan sakat/salung”. A rapid analytical technique to facilitate the evaluation of the P. malayana leaves’ quality has not been well-established yet. This work aimed therefore to develop a validated analytical technique in order to predict the alpha-glucosidase inhibitory action (AGI) of P. malayana leaves, applying a Fourier Transform Infrared Spectroscopy (FTIR) fingerprint and utilizing an orthogonal partial least square (OPLS). The dried leaf extracts were prepared by sonication of different ratios of methanol-water solvent (0, 25, 50, 75, and 100% v/v) prior to the assessment of alpha-glucosidase inhibition (AGI) and the following infrared spectroscopy. The correlation between the biological activity and the spectral data was evaluated using multivariate data analysis (MVDA). The 100% methanol extract possessed the highest inhibitory activity against the alpha-glucosidase (IC₅₀ 2.83 ± 0.32 μg/mL). Different bioactive functional groups, including hydroxyl (O-H), alkenyl (C=C), methylene (C-H), carbonyl (C=O), and secondary amine (N-H) groups, were detected by the multivariate analysis. These functional groups actively induced the alpha-glucosidase inhibition effect. This finding demonstrated the spectrum profile of the FTIR for the natural herb P. malayana Jack, further confirming its medicinal value. The developed validated model can be used to predict the AGI of P. malayana, which will be useful as a tool in the plant’s quality control. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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13 pages, 1969 KiB

Open AccessArticle

Potential Anti-Diabetic Activity of Pueraria lobata Flower (Flos Puerariae) Extracts

by Pattawika Lertpatipanpong, Sakawrat Janpaijit, Eul-Yong Park, Chong-Tai Kim and Seung Joon Baek

Molecules 2020, 25(17), 3970; https://doi.org/10.3390/molecules25173970 - 31 Aug 2020

Cited by 14 | Viewed by 4121

Abstract

Pueraria lobata (Wild.) Ohwi. (P. lobata) flowers known as ‘Kudzu flower’ contain isoflavonoids and essential oil components. They have a wide range of biological and pharmacological activities, including protective effects against non-alcoholic fatty liver disease, hyperglycemia, and hypolipidemia, anti-mutagenic effects, and [...] Read more.

Pueraria lobata (Wild.) Ohwi. (P. lobata) flowers known as ‘Kudzu flower’ contain isoflavonoids and essential oil components. They have a wide range of biological and pharmacological activities, including protective effects against non-alcoholic fatty liver disease, hyperglycemia, and hypolipidemia, anti-mutagenic effects, and benefits for weight loss. However, the molecular mechanism of these effects remains unclear. Our study aimed to systematically examine the effects of flos puerariae crude extract (FPE) as an anti-diabetic agent using in vitro assays. The cytotoxicity of FPE was evaluated using MTS assay in L6 rat myocyte and 3T3-L1 murine fibroblast cell lines. PPARγ binding activity and adipogenesis were examined using dual-luciferase and differentiation assays, respectively. For investigating the anti-diabetic activity, glucose utilization, including GLUT4 protein expression, glucose uptake assay, and GLUT4 translocation using immunofluorescence microscopy were conducted in L6 cells. Furthermore, we assessed the antioxidant and anti-inflammatory activities of FPE. Our results demonstrated the ability to augment glucose uptake in L6 cells and enhance glucose utilization activity by increasing the expression of glucose transporter type 4 (GLUT4). In summary, our findings suggest that FPE may be a potential anti-diabetic substance for the treatment of diabetic patients and can prevent inflammatory or oxidation-related diseases. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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Review

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31 pages, 1347 KiB

Open AccessReview

Diabetes and Cancer: Metabolic Association, Therapeutic Challenges, and the Role of Natural Products

by Wamidh H. Talib, Asma Ismail Mahmod, Sara Feras. Abuarab, Eliza Hasen, Amer A. Munaim, Shatha Khaled Haif, Amani Marwan Ayyash, Samar Khater, Intisar Hadi AL-Yasari and Lina T. Al Kury

Molecules 2021, 26(8), 2179; https://doi.org/10.3390/molecules26082179 - 10 Apr 2021

Cited by 14 | Viewed by 5009

Abstract

Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the [...] Read more.

Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base for researchers and physicians to test natural products as adjuvant alternative therapies to treat cancer in diabetic patients. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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77 pages, 4396 KiB

Open AccessReview

Middle East Medicinal Plants in the Treatment of Diabetes: A Review

by Alaa M. Abu-Odeh and Wamidh H. Talib

Molecules 2021, 26(3), 742; https://doi.org/10.3390/molecules26030742 - 31 Jan 2021

Cited by 32 | Viewed by 7477

Abstract

Diabetes is a global health problem, and the number of diabetic patients is in continuous rise. Conventional antidiabetic therapies are associated with high costs and limited efficiency. The use of traditional medicine and plant extracts to treat diabetes is gaining high popularity in [...] Read more.

Diabetes is a global health problem, and the number of diabetic patients is in continuous rise. Conventional antidiabetic therapies are associated with high costs and limited efficiency. The use of traditional medicine and plant extracts to treat diabetes is gaining high popularity in many countries. Countries in the Middle East region have a long history of using herbal medicine to treat different diseases, including diabetes. In this review, we compiled and summarized all the in vivo and in vitro studies conducted for plants with potential antidiabetic activity in the Middle East region. Plants of the Asteraceae and Lamiaceae families are the most investigated. It is hoped that this review will contribute scientifically to evidence the ethnobotanical use of medicinal plants as antidiabetic agents. Work has to be done to define tagetes, mechanism of action and the compound responsible for activity. In addition, safety and pharmacokinetic parameters should be investigated. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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14 pages, 575 KiB

Open AccessReview

β-Carotene: Preventive Role for Type 2 Diabetes Mellitus and Obesity: A Review

by Gabriela Marcelino, David Johane Machate, Karine de Cássia Freitas, Priscila Aiko Hiane, Iriani Rodrigues Maldonade, Arnildo Pott, Marcel Arakaki Asato, Camila Jordão Candido and Rita de Cássia Avellaneda Guimarães

Molecules 2020, 25(24), 5803; https://doi.org/10.3390/molecules25245803 - 09 Dec 2020

Cited by 47 | Viewed by 6124

Abstract

Carotenoids are vital antioxidants for plants and animals. They protect cells from oxidative events and act against the inflammatory process and carcinogenesis. Among the most abundant carotenoids in human and foods is β-carotene. This carotenoid has the highest level of provitamin A activity, [...] Read more.

Carotenoids are vital antioxidants for plants and animals. They protect cells from oxidative events and act against the inflammatory process and carcinogenesis. Among the most abundant carotenoids in human and foods is β-carotene. This carotenoid has the highest level of provitamin A activity, as it splits into two molecules of retinol through the actions of the cytosolic enzymes: β-carotene-15,15′-monooxygenase (β-carotene-15,15′-oxygenase 1) and β-carotene-9′,10′-dioxygenase (β-carotene-9′,10′-oxygenase 2). The literature supports the idea that β-carotene acts against type 2 diabetes mellitus, cardiovascular diseases, obesity, and metabolic syndrome. Due to the many processes involved in β-carotene biosynthesis and metabolic function, little is known about such components, since many mechanisms have not yet been fully elucidated. Therefore, our study concisely described the relationships between the consumption of carotenoids, with emphasis on β-carotene, and obesity and type 2 diabetes mellitus and its associated parameters in order to understand the preventive role of carotenoids better and encourage their consumption. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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19 pages, 1076 KiB

Open AccessReview

Regulation of Obesity by Antiangiogenic Herbal Medicines

by Soon Shik Shin and Michung Yoon

Molecules 2020, 25(19), 4549; https://doi.org/10.3390/molecules25194549 - 04 Oct 2020

Cited by 14 | Viewed by 3776

Abstract

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought [...] Read more.

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought to be associated with angiogenesis and extracellular matrix (ECM) remodeling. Angiogenesis occurs in growing adult adipose tissues, which are similar to neoplastic tissues. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network. Adipocytes produce proangiogenic factors, such as vascular endothelial growth factor A and fibroblast growth factor 2, which promote neovascularization within the adipose tissue. Furthermore, matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, play important roles in adipose tissue development and microvessel maturation by modifying the ECM. Thus, modulation of angiogenesis and MMP activity provides a promising therapeutic approach for controlling human obesity and its related disorders. Over the past decade, there has been a great increase in the use of alternative treatments, such as herbal remedies, for these diseases. This review will focus on the role of angiogenesis in adipose tissue growth and the regulation of obesity by antiangiogenic herbal medicines. Full article

(This article belongs to the Special Issue Natural Products for the Treatment of Diabetes and Obesity)

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