Netala Vasudeva Reddy, Hou Tianyu, Devarapogu Rajakumari, Bethu Murali Satyanarayana, Zhang Zhijun, Vijaya Tartte
Department of Biotechnology, Sri Venkateswara University, Tirupati, A.P, 517502, India.
School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, 030051, China.
Heliyon. 2024 Nov 30;10(23):e40850. doi: 10.1016/j.heliyon.2024.e40850. eCollection 2024 Dec 15.
The study comprehensively investigated the therapeutic potential of 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.
该研究全面考察了三萜皂苷提取物（GST）的治疗潜力，包括其肝脏保护、免疫调节和抗癌活性。该研究采用泼尼松龙（PRD）诱导的免疫抑制大鼠模型来评估GST的肝脏保护和免疫调节作用。利用该模型，发现GST可调节造血功能，改善红细胞、血小板和白细胞计数，突出了其在造血稳态中的潜力。脾脏、胸腺、肝脏和肾脏中作为免疫抑制标志的器官萎缩，经GST治疗后得到逆转，增强了其肝营养和器官亲和能力。包括丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和脂质过氧化物酶（LPO）在内的肝脏生物标志物升高，表明肝细胞损伤和氧化应激，经GST处理后降低，突出了其肝脏保护和抗氧化作用。此外，GST恢复了耗尽的抗氧化剂谷胱甘肽（GSH）和超氧化物歧化酶（SOD），突出了其强大的抗氧化能力。分子研究表明，免疫抑制大鼠脾脏中白细胞介素-2（IL-2）和白细胞介素-4（IL-4）mRNA下调，而GST治疗显著上调IL-2和IL-4 mRNA表达，展示了其免疫调节潜力。与免疫失调相关的肿瘤坏死因子-α（TNF-α）水平升高被GST有效降低，突出了其在调节炎症反应和恢复免疫平衡中的作用。分子对接研究表明GST化合物对TNF-α有强烈抑制作用。在抗癌活性方面，GST对MCF-7和MDA-MB-231（乳腺癌细胞系）表现出显著的细胞毒性。值得注意的是，GST与正常的中国仓鼠卵巢细胞系（CHO）和人脐静脉内皮细胞系（HUVEC）具有生物相容性。分子对接研究表明GST化合物对乳腺癌蛋白HER1和HER2（人表皮生长因子受体）有强烈抑制作用。此外，药代动力学、生物利用度、药物相似性和毒性风险预测表明，GST化合物在药理学上是有利的，没有不良反应。
