Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics
The study comprehensively investigated the therapeutic potential of Gymnema sylvestre triterpenoid saponin extract (GST), encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone (PRD)-induced immunosuppressed rat model to assess the hepatopro...
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Elsevier
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024168818 |
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| author | Vasudeva Reddy Netala Tianyu Hou Rajakumari Devarapogu Murali Satyanarayana Bethu Zhijun Zhang Tartte Vijaya |
| author_facet | Vasudeva Reddy Netala Tianyu Hou Rajakumari Devarapogu Murali Satyanarayana Bethu Zhijun Zhang Tartte Vijaya |
| author_sort | Vasudeva Reddy Netala |
| collection | DOAJ |
| description | The study comprehensively investigated the therapeutic potential of Gymnema sylvestre triterpenoid saponin extract (GST), encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone (PRD)-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of GST. Using this model, GST was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, thymus, liver, and kidneys, was reversed with GST treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers, including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lipid peroxidase (LPO), indicative of hepatocellular injury and oxidative stress, were reduced with GST, underscoring its hepatoprotective and antioxidative effects. Additionally, GST restored depleted antioxidants glutathione (GSH) and superoxide dismutase (SOD), highlighting its strong antioxidative capabilities. Molecular insights revealed a downregulation of interleukin-2 (IL-2) and interleukin-4 (IL-4) mRNA in the spleen of immunosuppressed rats, while GST treatment significantly upregulated IL-2 and IL-4 mRNA expression, showcasing its immunomodulatory potential. Increased levels of tumor necrosis factor-α (TNF-α) associated with immune dysregulation were effectively decreased by GST, underscoring its role in modulating inflammatory responses and restoring immune balance. Molecular docking studies indicated strong inhibition of TNF-α by GST compounds. In terms of anticancer activity, GST demonstrated significant cytotoxicity against MCF-7, and MDA-MB-231 (breast cancer cell lines). Notably, GST demonstrated biocompatibility with normal CHO (Chinese hamster ovary cell line) and HUVEC (Human umbilical vein endothelial cells) cell lines. Molecular docking studies indicated strong inhibition of breast cancer proteins HER1 and HER2 (human epidermal growth factor receptors) by GST compounds. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk predictions suggest that GST compounds are pharmacologically favourable with no adverse effects. |
| format | Article |
| id | doaj-art-8a3f10b032ea4883b579784a5c8b8dba |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-8a3f10b032ea4883b579784a5c8b8dba2024-12-13T10:59:59ZengElsevierHeliyon2405-84402024-12-011023e40850Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokineticsVasudeva Reddy Netala0Tianyu Hou1Rajakumari Devarapogu2Murali Satyanarayana Bethu3Zhijun Zhang4Tartte Vijaya5Department of Biotechnology, Sri Venkateswara University, Tirupati, A.P, 517502, India; School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, 030051, China; Corresponding author. Department of Biotechnology, Sri Venkateswara University, Tirupati, A.P, 517502, India.School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, 030051, ChinaDepartment of Zoology, Sri Venkateswara University, Tirupati, A.P, 517502, IndiaDepartment of Toxicology and Cancer Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, IndiaSchool of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, 030051, ChinaDepartment of Botany, Sri Venkateswara University, Tirupati, A.P, 517502, India; Corresponding author.The study comprehensively investigated the therapeutic potential of Gymnema sylvestre triterpenoid saponin extract (GST), encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone (PRD)-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of GST. Using this model, GST was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, thymus, liver, and kidneys, was reversed with GST treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers, including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lipid peroxidase (LPO), indicative of hepatocellular injury and oxidative stress, were reduced with GST, underscoring its hepatoprotective and antioxidative effects. Additionally, GST restored depleted antioxidants glutathione (GSH) and superoxide dismutase (SOD), highlighting its strong antioxidative capabilities. Molecular insights revealed a downregulation of interleukin-2 (IL-2) and interleukin-4 (IL-4) mRNA in the spleen of immunosuppressed rats, while GST treatment significantly upregulated IL-2 and IL-4 mRNA expression, showcasing its immunomodulatory potential. Increased levels of tumor necrosis factor-α (TNF-α) associated with immune dysregulation were effectively decreased by GST, underscoring its role in modulating inflammatory responses and restoring immune balance. Molecular docking studies indicated strong inhibition of TNF-α by GST compounds. In terms of anticancer activity, GST demonstrated significant cytotoxicity against MCF-7, and MDA-MB-231 (breast cancer cell lines). Notably, GST demonstrated biocompatibility with normal CHO (Chinese hamster ovary cell line) and HUVEC (Human umbilical vein endothelial cells) cell lines. Molecular docking studies indicated strong inhibition of breast cancer proteins HER1 and HER2 (human epidermal growth factor receptors) by GST compounds. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk predictions suggest that GST compounds are pharmacologically favourable with no adverse effects.http://www.sciencedirect.com/science/article/pii/S2405844024168818Gymnema sylvestreTriterpenoid saponin extractHepatoprotectiveAntioxidantImmunomodulatoryAnticancer |
| spellingShingle | Vasudeva Reddy Netala Tianyu Hou Rajakumari Devarapogu Murali Satyanarayana Bethu Zhijun Zhang Tartte Vijaya Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics Heliyon Gymnema sylvestre Triterpenoid saponin extract Hepatoprotective Antioxidant Immunomodulatory Anticancer |
| title | Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics |
| title_full | Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics |
| title_fullStr | Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics |
| title_full_unstemmed | Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics |
| title_short | Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics |
| title_sort | exploring the therapeutic potential of triterpenoid saponins from gymnema sylvestre mechanistic insights into hepatoprotection immunomodulation anticancer activities molecular docking and pharmacokinetics |
| topic | Gymnema sylvestre Triterpenoid saponin extract Hepatoprotective Antioxidant Immunomodulatory Anticancer |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024168818 |
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