The dichloromethane fraction from Calotropis gigantea (L.) dryand. Stem bark extract prevents liver cancer in SDT rats with insulin-independent diabetes mellitus.

Autor: Haewphet T; Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: thaiyawath64@nu.ac.th., Parhira S; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand; Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: supawadeep@nu.ac.th., Chaisupasakul P; Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: pattarapornc63@nu.ac.th., Wangteeraprasert A; Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: apirathw@nu.ac.th., Phoungpetchara I; Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: ittiponp@nu.ac.th., Pekthong D; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand; Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: dumrongsakp@nu.ac.th., Kaewkong W; Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: worasakk@nu.ac.th., Jiang ZH; State Key Laboratory of Quality Research in Chinese Medicine, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, China. Electronic address: zhjiang@must.edu.mo., Bai LP; State Key Laboratory of Quality Research in Chinese Medicine, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, China. Electronic address: lpbai@must.edu.mo., Somran J; Department of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: julintorns@nu.ac.th., Srisawang P; Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand. Electronic address: piyarats@nu.ac.th.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Nov 15; Vol. 334, pp. 118516. Date of Electronic Publication: 2024 Jul 04.
DOI: 10.1016/j.jep.2024.118516
Abstrakt: Ethnopharmacological Relevance: Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments.
Aim: This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy.
Materials and Methods: Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression.
Results: Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-β1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage.
Conclusions: These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.
Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose. All authors have approved of the final article.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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