Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

Abstract

BackgroundWhile all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated.MethodsIn alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB) activation induced by IL-1β and IFN-γ was investigated.ResultsIn alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation.ConclusionWe have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

Beneficial effects of anAndrographis paniculataextract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats

“…Andrographolide modulates physiological functions of diverse drug metabolising enzymes in liver and other peripheral organs as well (Pekthong et al 2008), and binds covalently with cellular metabolites and enzymes (Xia et al 2004). Andrographolide-lipoic acid conjugate possesses andrographolide like and longer lasting antidiabetic activity in mice (Zhang et al 2009). Therefore, it could as well be that the observed beneficial effects of andrographolide on memory functions and AChE and antioxidative enzymes in the brain observed in this study are due to its conjugates.…”

Anti-tumor Initiating Potential of Andrographolide in 7,12-dimethylbenz[a]anthracene Induced Hamster Buccal Pouch Carcinogenesis

“…Andrographolide, natural bicyclic diterpenoid lactones, is an active constituent of Andrographis paniculata. Experimental studies demonstrated diverse pharmacological effects of andrographolide including anti-inflammatory, antihyperglycemic, hepatoprotective and anticancer properties (Lin et al, 2009;Zhang et al, 2009). Previous studies from our laboratory demonstrated the antigenotoxic, pro-apoptotic and anti-inflammatory potential of andrographolide in experimental animal models Shanmugam et al, 2012).…”

PEMANFAATAN BAKTERI ENDOFIT DAN FOSFAT UNTUK PERTUMBUHAN DAN PRODUKSI TANAMAN SAMBILOTO / Utilizing Endophytic Bacteria and Phosphate for Growth and Yieald of Andrographis paniculata

“…Sambiloto merupakan salah satu tanaman obat yang mempunyai banyak khasiat antara lain sebagai anti diabetes (ZHANG et al, 2009), anti mikrob (XU et al, 2006), anti kanker (CHENG et al, 2007). Tanaman sambiloto mengandung beberapa senyawa kimia antara lain terpenoid, flavonoid, alkane, keton, aldehid, mineral (kalium, kalsium, natrium), asam kersik, dan dammar (RAO et al, 2004).…”