Studies on Anti-inflammatory and Anti-diabetic Potential of Andrographolide: Evidence from an In vitro, In silico and In vivo Study (original) (raw)
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Indonesian Journal of Biotechnology, 2022
Andrographolide has been shown to have a pharmacological effect as an antidiabetic. Nevertheless, the comprehensive mechanism of action has yet to be determined. Andrographolide is a primary component of the sambiloto herb (Andrographis paniculata (Burm.f.) Nees), in which a simple isolation process can obtain high yields. This study aimed to explain the anti-diabetic effect of andrographolide compared to pioglitazone (a positive control) on glucose uptake by measuring the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT-4) genes in 3T3-LI mouse adipocytes as an in vitro model. The differentiation of mature adipocytes from 3T3-L1 fibroblasts was induced with 3-isobutyl-1-methylxanthine, dexamethasone, and insulin. Andrographolide was provided through direct isolation from A. paniculata herbs. The gene expression was detected using the reverse transcriptionpolymerase chain reaction (RT-PCR). Pioglitazone and andrographolide significantly increased glucose uptake capability. Andrographolide was able to increase the mRNA levels of PPARγ and GLUT-4 compared to pioglitazone with the best concentration at 5.6 µM. In conclusion, andrographolide can improve glucose uptake by increasing mRNA levels of PPARγ and GLUT-4 that encodes protein, which are key factors for glucose homeostasis. Therefore, this finding further establishes the potency of andrographolide from A. paniculata as an antidiabetic.
Journal of Ethnopharmacology, 2011
Ethnopharmacological significance: Inflammation is involved in numerous diseases, such as chronic inflammatory disease and cancer. Many plant products exhibit useful biological activities, including antifungal, antibacterial, and anti-inflammatory actions. Aim of study: However, our understanding of the anti-inflammatory effects of andrographolide is limited. Materials and methods: We use lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of andrographolide, which contains polyphenolic structures. Results: We found that andrographolide exhibited a potent anti-inflammatory effect. In this study, we investigated the inhibitory effects of andrographolide on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) as well as their respective downstream products, NO and PGE2, in RAW264.7 cells treated with LPS. Treatment with andrographolide also reduced nuclear factor-B (NF-B) and activation protein-1 (AP-1) DNA-binding activity. Western blot analysis showed that andrographolide significantly inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and the protein expression of CCAAT/enhancer-binding protein ␦ (C/EBP␦). We also found that andrographolide suppressed LPS-induced suppressor of cytokine signalling 1 and 3 (SOCS1 and 3) mRNA expression, which, in turn, inhibited apoptosis signalling and mitochondria membrane potential activation. Our results demonstrate that andrographolide downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-B and STAT3 by interfering with the expression of SOCS1 and SOCS3 signalling. Conclusion: Therefore, andrographolide exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.
Biomedicine & Pharmacotherapy, 2017
The prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is increasing and there is an increasing interest in natural products to treat NAFLD. This study aimed to evaluate the hepatoprotective effect of andrographolide and two of its derivatives; in one the OH group at C-14 was removed and in the other OH groups at C-3 and C-19 were protected. Andrographolide (AN) was isolated from the aerial parts of Andrographis paniculata Wall. Isoandrographolide (IAN) and 3,19-acetonylidene andrographolide (ANA) were derivatized from AN. Drug likeness of the compounds was studied using DataWarrior. The effect of the compounds in ameliorating hepatic steatosis and lipotoxicity was assessed using palmitate-oleate induced steatotic HepG2 cell lines. In vivo efficacy of the compounds was assessed by using HFD fed rats. IAN showed comparatively high drug score and low irritability than AN. MTT assay indicated that the treatment with IAN had comparatively less toxicity than AN and ANA to HepG2 cells. The treatment with IAN significantly reduced the lipid accumulation and the leakage of LDH and transaminases, while the treatments with AN and ANA did not prohibit the leakage. In the in vivo experiment, the treatment with IAN showed comparatively better hepatoprotection by reducing the serum lipid, transaminases and ALP levels than with AN and ANA. Our results showed that IAN could be a promising lead to treat NAFLD with comparatively low toxicity and improved efficacy.
Journal of Ethnopharmacology, 2010
Ethnopharmacological relevance: Extracts of Andrographis paniculata Nees are used for various ethnomedical conditions including hyperglycemia and hypertension complications. Aim of the study: The purpose of this study is to evaluate the anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata. Materials and methods: MES-13, a SV40-transformed murine glomerular mesangial cell line, was cultured in high concentration of glucose to induce diabetic nephropathy phenotypes, which include secretion of extracellular matrix protein fibronectin, cytokine TGF-, states of oxidative stress, and apoptosis marker caspase-3. Results: Our data suggest that addition of compounds AP1 or AP2 reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker caspase-3, fibrosis marker TGF-, and PAI-1. Furthermore, AP1 and AP2 do not have antioxidant ability in acellular environment; however, addition of AP1 and AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells. Conclusion: This is the first report on anti-diabetic nephropathy effect of AP1 and AP2 in part due to the regulation of intracellular signaling transduction, not mere clearance of reactive oxygen species. Thus, this study may be useful for drug development or food supplement for diabetes and nephropathy from Andrographis paniculata.
Evidence-Based Complementary and Alternative Medicine, 2013
Andrographolide (AG) is an abundant component of plants of the genusAndrographisand has a number of beneficial properties including neuroprotective, anticancer, anti-inflammatory, and antidiabetic effects. Despite numerous pharmacological studies, the precise mechanism of AG is still ambiguous. Thus, in the present study, we investigated the molecular mechanisms of AG and its target proteins as they pertain to anti-inflammatory responses. AG suppressed the production of nitric oxide (NO) and prostaglandin E2(PGE2), as well as the mRNA abundance of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX)-2, and interferon-beta (IFN-β) in a dose-dependent manner in both lipopolysaccharide- (LPS-) activated RAW264.7 cells and peritoneal macrophages. AG also substantially ameliorated the symptoms of LPS-induced hepatitis and EtOH/HCl-induced gastritis in mice. Based on the results of luciferase reporter gene assays, kinase assays, and measurement of nuclea...
Pharm Biol, 2008
Andrographis paniculata (Burm.f.) Nees (Acanthaceae) (AP), containing the major active principle, andrographolide,(AG) has been used ethnomedically in the treatment of diabetes and hypertension in Malaysia and India. Type 2 diabetes mellitus was induced by administering nicotinamide (NA) 180 mg/kg i.p., followed by streptozotocin (STZ) 45 mg/kg i.p., 15 min later and allowed for 15 days to develop. Diabetic rats treated with active principle andrographolide 10 mg/kg and ethanol extract of Andrographis paniculata at doses of 500 and 1000 mg/kg, p.o, for 21 days, caused a significant reduction in fasting serum glucose levels on all days analysed (P < 0.01). Treatment with andrographolide and extract showed an increase in glucokinase (GK; P < 0.05), hexokinase (HK; P < 0.05), and lactate dehydrogenase (LDH; P < 0.05) enzyme levels respectively. Significant reductions were observed in serum cholesterol (P < 0.05), triglycerides (P < 0.05), free fatty acids (P < 0.05), and liver glucose 6-phosphatase (G6P'Tase; P < 0.05) enzyme levels on treatment with andrographolide and extract. Glucose 6-phosphate dehydrogenase (G6PDH; P < 0.05) level also showed a significant increase on treatment with andrographolide and extract. Liver antioxidant status (P < 0.05) also improved significantly on treatment with andrographolide and extract. However, no significant increase in serum insulin was found on treatment with either andrographolide or extract, suggesting an effective extra pancreatic mechanism. Thus, the present study demonstrates that andrographolide at 10 mg/kg, and ethanol extract of Andrographis paniculata at 500 and 1000 mg/kg, p.o., on treatment for 21 days,
Andrographolide a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease
InTech eBooks, 2013
Andrographis paniculata, (Burm. f.) Wall. ex Nees, a herbaceous plant belonging to the Family Acanthaceae, is one of the most commonly used medicinal plants in the traditional systems of Unani and Ayurvedic medicines. It grows in hedge rows throughout the plains of India and is also cultivated in gardens. It also grows in many other Asian countries and is used as a traditional herbal medicine in China, Hong Kong, the Philippines, Malaysia, Indonesia, and Thailand. It is an annual plant of 1-3 ft high, also known as the "king of bitters", being the aerial parts most commonly used. A. paniculata have shown a broad range of pharmacological effects such as inhibition of replication of the HIV virus, prevention of common cold, and antimalarial, antidiarrheal, antibacterial, antihyperglycemic effects, suppression of various cancer cells, and principally anti-inflammatory properties. Andrographolide is the major labdane diterpenoid isolated from A. paniculata and exhibits anti-inflammatory and anticancer activities, either in vitro or in vivo experimental models of inflammation and cancer. Several immunomodulatory responses of andrographolide have been observed in in vitro studies, such as reduction of iNOS, COX-2, NO, PGE2, TNF-alpha and IL-12 in macrophages and microglia. In neutrophils is able to reduce the radical oxygen species production, and Mac-1, IL-8 and COX-2 expression. In T cells, andrographolide inhibits the expression of IL-2, IFNγ and IL-6, reducing the humoral and cellular adaptive immune response. Andrographolide was able to reduce the dendritic cells maturation and their ability to present antigens to T cells. Andrographolide administered in rodents reduced the Th2 cytokine IL-4, IL-5, IL-13 and serum immunoglobulin in an ovalbumin induced asthma model. A reduction of T cells response also has been observed in experimental autoimmune encephalomyelitis and systemic lupus erythematosus mouse model. Several of immunomodulatory responses have been associated to the inhibition of Nuclear Factor-κB
In vitro and in vivo antidiabetic effect of Andrographis
Wt.Ic leaf extracts Andrographis lineata and Andrographis serphyllifolia are endemic potential medicinal plants of South India. The leaves of both the herbs have been used as ancient folklore medicine for curing diabetes, snakebite, inflammation and cancer. The present investigation deals with the study of in vitro and in vivo antidiabetic effect of the ethanolic leaf extract of A. lineata (EtALL) and ethanolic leaf extract of A. serphyllifolia (EtASL). Qualitative analysis of phytochemicals revealed the presence of alkaloids, tannins, terpenoids, steroids, flavanoids and polyphenol compounds, absence of saponins and steroids in both the extracts. The α-glucosidase inhibition results of EtALL (IC 50 value 10.12 µg/ml) and EtASL (IC 50 value 11.39 µg/ml) exhibited stronger inhibitory activity for α-glucosidase which was comparable with Acarbose. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay of the EtALL and EtASL extracts in 3T3-L1cell line confirmed that there was no toxicity effect for both the extracts from 6.5 to 50 µg/ml concentrations. The glucose uptake rate in 3T3-L1 cells revealed the fact that both the extracts showed increase in glucose uptake rate in dose dependent manner comparable to insulin. Further these extracts were evaluated in the in vivo model to prove the traditional claim of usage pertaining to antidiabetic property. The acute toxicity studies showed that there was no death or lethal effect observed in toxicity study. The acute treatment of fasting blood sugar and oral glucose tolerance test of EtALL and EtASL extract (400 mg/kg b.w.) treated normoglycemic rats showed hypoglycemic effect. When the streptozotocin induced diabetic rats was administered with EtALL and EtASL 400 mg/kg b.w. in chronic model (28 days) there was a significant reduction in plasma glucose, plasma insulin level, total cholesterol, low density lipoprotein (LDL)-C triglyceride, glucose-6phosphatase and fructose -1, 6-bisphosphatase levels. Glycogen content (liver and muscle), high density lipoprotein (HDL) cholesterol, hexokinase, was significantly increased compared with the diabetic control rats in both the extracts treated rats. The above findings showed the significant antidiabetic potential of the extracts in ameliorating the diabetic condition in the diabetic treated rats. Further studies are in progress to identify the active principle's possible for the antidiabetic effect in EtALL and EtASL extracts.