Protective Effect Of Andrographolide Research Articles

Protective effects of andrographolide against diclofenac-induced gastric damage

The use diclofenac in pain management is limited by the development of gastric ulcers. Andrographolide is a clinically approved medicinal plant extract that has been found to possess among others, a gastro protective effect and may therefore be useful in protecting against damaging effects of diclofenac. The research study aimed at determining the gastro-protective effect of andrographolide in the presence of diclofenac. Two rodent models of gastro-protection were used in this study. In the mouse pyloric ligation model, effect of andrographolide alone and in combination with diclofenac on secretion of gastric contents was determined. In the acute gastritis model, effects of andrographolide on diclofenac induced ulcers in rats was evaluated. Haematoxylin and Eosin (H&E) stain was used in histopathological examination in the acute gastritis model. All statistical analysis was done using one way analysis of variance.In the mouse pyloric ligation model, diclofenac treatment significantly lowered the pH (1.46 ± 0.1453 compared to ligated controls 3.30 ± 0.0577, p < 0.05), and co-administration of diclofenac with andrographolide raised it significantly (pH of 4.80 ±0.3512 in combination compared to diclofenac only treated groups with pH of 1.46 ± 0.1453, p < 0.001). The standard anti-ulcer drug, esomeprazole also produced a similar elevation in pH (3.87 ± 0.2848 for esomeprazole compared to diclofenac only treated groups with pH of 1.46 ±0.1453, p < 0.01). Esomeprazole and andrographolide also reduced the mucosal damaging effects of diclofenac in the acute gastritis model in rats with a reduction in the number of ulcers produced (esomeprazole 50 mg/kg, 1.0 ± 0.6000, p < 0.0001 and andrographolide 100 mg kg/kg, 2.0 ± 0.6000, p < 0.001 compared to vehicle treated groups, 10.0 ± 1.095). Histopathological examination showed reduction in damaging effects of diclofenac after andrographolide and esomeprazole administration.Results show andrographolide possesses gastro-protective effect in the presence of diclofenac.

Protective effects of andrographolide against cerebral ischemia‑reperfusion injury in mice.

Ischemic stroke is one of the most common causes of mortality worldwide and is a primary cause of disability and mortality in adults. There is an unmet need for drugs that can effectively treat ischemic stroke. Hence, the present study explored the neuroprotective effects of andrographolide (Andro) in a mouse model of bilateral common carotid artery occlusion, and systematically evaluated the potential mechanisms underlying its effects. The effects of Andro on mouse brain tissue following cerebral ischemia-reperfusion injury (CIRI) were evaluated by histopathological (H&E and Nissl) and immunofluorescence [glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN)] staining. A traditional Chinese medicine-based network pharmacology method was performed to establish and analyze compound-target-disease and function-pathway networks in order to elucidate the possible mechanisms responsible for the protective role of Andrographis paniculata in CIRI. In addition, western blot analysis and RT-qPCR was performed to evaluate the expression and activation of signaling proteins predicted to be involved in this mechanism. The amelioration of histopathological alterations was observed in mice pre-treated with Andro. Immunofluorescence staining revealed that Andro decreased the expression of GFAP and increased the expression of NeuN, and significantly decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α). Network pharmacology analysis revealed that neuroinflammatory response and apoptosis were associated with the effects of Andrographis paniculata on CIRI. Western blot analysis revealed that the mice pre-treated with Andro exhibited an upregulated protein expression of tropomyosin receptor kinase B (TrkB), p-PI3K and p-Akt, as well as a decrease in the expression of GFAP and an increase in the expression of NeuN. In addition, the data of RT-qPCR indicated that the mice pre-treated with Andro exhibited a significantly decreased expression of encoding IL-1β mRNA, IL-6 mRNA and TNF-α mRNA in the brain compared to the untreated mice following CIRI. On the whole, the findings of the present study suggest that pre-treatment with Andro exerts a protective effect against CIRI, which may be partly related to its potential to reduce neuroinflammatory response and apoptosis in patients with stroke.

Effects of andrographolide on renal tubulointersticial injury and fibrosis. Evidence of its mechanism of action

BackgroundDiabetic nephropathy (DN) is associated with renal interstitial injury and fibrosis. Our previous study showed that andrographolide protected against the progression of DN and high glucose (HG)-induced mesangial dysfunction. However, the protective effects of andrographolide on renal tubular epithelial cells have not been fully elucidated. PurposeTo determine the protective effects of andrographolide on renal tubular damage and explore the underlying mechanism. Study designHuman tubular epithelial cells (HK-2 cells) were treated with andrographolide (5 and 10 μM) under HG conditions. Diabetic mice were treated with andrographolide (i.p. 2 and 4 mg/kg, twice per week). MethodsWestern blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence and flow cytometry were used to analyze the effects of andrographolide on renal tubular injury and fibrotic mechanisms in HK-2 cells. The protective effects of andrographolide against renal tubulointerstitial injury and fibrosis were investigated in diabetic mice fed a high-fat diet (HFD). Renal interstitial tissue was collected at sacrifice for immunohistochemistry, immunofluorescence analysis, RT-PCR and Western blotting to analyze the effects of andrographolide on renal tubular injury and fibrosis. ResultsIn vitro assay results indicated that andrographolide (5 and 10 μM) effectively inhibited HG-induced apoptosis, epithelial-mesenchymal transition (EMT) and collagen deposition in HK-2 cells. Mechanistically, HG stimulated mitochondrial reactive oxygen species (mtROS)-mediated NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and EMT in tubular epithelial cells, and andrographolide (5 and 10 μM) inhibited these effects by ameliorating mitochondrial dysfunction. In vivo, treatment with andrographolide (2 and 4 mg/kg) inhibited renal tubular cell apoptosis, EMT and tubulointerstitial fibrosis, mitochondrial dysfunction and NLRP3 inflammasome activation in diabetic mice. ConclusionAndrographolide (5 and 10 μM) prevents HG-induced renal tubular cell damage, and andrographolide (2 and 4 mg/kg) protects against the progression of diabetic tubular injury and fibrosis in mice by suppressing mitochondrial dysfunction and NLRP3 inflammasome activation.

Protective effect of andrographolide against STZ induced Alzheimer's disease in experimental rats: possible neuromodulation and Aβ(1-42) analysis.

STZ is a glucosamine-nitrosourea compound, causes dysfunctioning of insulin receptors in the brain and disrupts glucose metabolism, produces cognitive decline and AD-like symptoms. ICV injection of STZ causes accumulation of Aβ and cognitive dysfunctions. Andrographolide (ANDRO) is a major bioactive constituent of Andrographis paniculata, has various biological activities such as antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties. The study aimed to evaluate the neuroprotective effect of ANDRO against ICV-STZ induced AD-like symptoms in rats. To conduct the study, the Wistar rat received two injections of STZ (3mg/kg) through the ICV route. Rats were treated with three different doses of ANDRO (15, 30, and 60mg/kg, p.o.) and donepezil (5mg/kg, p.o.) for 14days. The behavioral impairments were analyzed on weekly basis. Subsequently, rats were sacrificed for the assessment of biochemical (MDA, Nitrite, GSH, SOD, Catalase and AChE), neuroinflammatory markers (IL-1β, IL-16, and TNF-α), neurotransmitters (glutamate and GABA), level of Aβ1-42 and p tau in the hippocampus on day 21st. Our result indicated that ANDRO treatment provided a protective effect against STZ induced behavioral deficits and changes in the biochemical, neuroinflammatory mediators, and neurotransmitters of the hippocampus. Further, ANDRO also reduced the level of Aβ1-42 and p tau in the rat hippocampus. These findings suggested that the antioxidant, anti-inflammatory, anti-cholinesterase potential of ANDRO contributed to its neuroprotective effect as well as promising therapeutic candidate for the treatment of cognitive impairment and AD-like symptoms.

Protective effect of Andrographolide on 5-Fu induced intestinal mucositis by regulating p38 MAPK signaling pathway

Aims: Intestinal mucositis is the most common side effect of 5-fluorouracil (5-Fu) treatment in cancer patients. Previous research suggested that andrographolide (Andro) attenuated the intestinal injury in colitis or diarrhea in mice. The present study was aimed at investigating the protective effect of Andro against 5-Fu induced intestinal mucositis and the underlying mechanism.Main methods: BALB/C mice were injected 5-Fu at a dose of 100 mg/kg for 5 days to induce intestinal mucositis. Andro at different doses (25, 50, 100 mg/kg/day) was administered. Weight loss, diarrhea score, cellular apoptosis and proliferation were evaluated. Apoptosis related proteins were detected by Western blotting. Then, NCM460 cells were used to explore the possible mechanism in vitro. The effect of Andro on the anti-tumor efficacy of 5-Fu was investigated in H22 tumor-bearing mice.Key findings: Andro significantly ameliorated the 5-Fu induced weight loss and diarrhea. The apoptosis of intestinal cells was also attenuated by Andro treatment both in vivo and in vitro. Besides, Andro markedly down-regulated the 5-Fu-induced protein expression of caspase8/3, Bax and the phosphorylation of p38. Moreover, 5-Fu significantly reduced the viability of NCM460 cells, which was restored by the Andro pretreatment. Furthermore, asiatic acid, an agonist of p38 MAPK, reversed the anti-apoptotic effect of Andro in NCM460 cells. Andro did not weaken the anti-H22 tumor effect of 5-Fu in vivo.Significance: We have demonstrated that p38 MAPK inhibition mediates anti-apoptotic effects of Andro against 5-Fu induced intestinal mucositis, suggesting that Andro may benefit the patients undergoing 5-Fu based chemotherapy.

Protective Effect of Andrographolide in 3-Nitropropionic Acid Induced Huntington Disease and Associated Neurodegenerative Changes in Rats

Aims: Oxidative stress and activation of pro-apoptotic mediators have been associated with the pathogenesis of Huntington’s disease. Andrographolide (ANDRO) is a well-known antioxidant and inhibitor of pro-apoptotic mediator, nuclear factor kappa B (NF-kB).&#x0D; Study Design: The present study was hence designed to evaluate the effect of ANDRO in Huntington’s disease.&#x0D; Place and Duration of Study: Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India between March 2018 and July 2018.&#x0D; Methodology: Five groups (n=6) of Sprague dawley rats were used. Normal group animals were kept untreated. The control group was administered 3-Nitro propionic acid (3-NP) for seven days. The three treament groups received 3-NP followed by ANDRO intraperitoneally for seven days. On 8th day, behavioral and coordination parameters were evaluated using multiple tests. Oxidative stress and anti-oxidant enzyme levels in brain tissue were also evaluated. Brain tissues were also evaluated using Haematoxylin-eosin staining.&#x0D; Results: Administration of 3-NP resulted in motor incoordination and muscle weakness as indicated by behavioral tests. Biochemically, there was an increase in the oxidative stress and depletion of free radical scavenging. Histopathologically, there was severe neuronal degeneration and neural tissue apoptotic changes in the rat striatum. ANDRO administration resulted in significant decrease in the muscle incoordination in the behavioral tests and also decreased prooxidative biochemical changes. Brain tissues of the ANDRO treated animals showed protection against neuronal damage and neurodegeneration.&#x0D; Conclusion: The results indicate that the use of ANDRO may afford protection against Huntington’s disease associated muscle incoordination and subsequent neurodegeneration. Present study provides a lead for further investigation of role of NF-kB inhibitors in Huntington’s disease and possible development of low-cost natural medication.

Protective Effect of Andrographolide on Alleviating Chronic Alcoholic Liver Disease in Mice by Inhibiting Nuclear Factor Kappa B and Tumor Necrosis Factor Alpha Activation.

Much research has indicated that alcoholic liver disease (ALD) is associated with oxidative stress and inflammation induced by ethanol, and that numerous antioxidants could effectively alleviate such injuries. Moreover, recent studies have identified andrographolide (AD) as having strong anti-inflammatory and antioxidant activities, which can block oxidative damage associated with nuclear factor kappa B (NF-κB)-mediated inflammation. However, the biological role and potential mechanism of AD in its protection against ALD have not been fully characterized. To observe the possible effect of AD, male C57BL/6J mice received ethanol through intragastrical gavage for 12 weeks in this study. The ethanol group was separated into five subgroups: (1) model group (n = 10); (2) silymarin group (0.1 mg/g body weight [BW], n = 10); (3) AD (0.05 mg/g BW) group (n = 10); (4) AD (0.1 mg/g BW) group (n = 10); and (5) AD (0.2 mg/g BW) group (n = 10). Mice in AD groups were treated orally by gavage once per day. The experimental results show that serum aminotransferase, liver lipids, lipid peroxidation, and antioxidant capacities were significantly changed in the model group after alcohol treatment, and the liver tissue histological findings showed pathological changes. Compared with the model group, treatment with AD improved serum aminotransferase, liver function, lipid accumulation, and hepatic reactive oxygen species levels. And AD decreased the hepatic NF-κB and tumor necrosis factor alpha (TNF-α) protein expression of ALD mice. This research demonstrated that AD can alleviate liver pathological injury and oxidative stress in mice exposed to ethanol by decreasing the expression of NF-κB and TNF-α.

Protective effects of andrographolide on septic mice and the related mechanism

Objective To investigate the protective effects of andrographolide on septic mice and to explore the underlying mechanism.Methods Sepsis model was induced by cecal ligation and puncture(CLP)in mice.A total of 64C57BL/6mice were evenly randomized into 4 groups:a sham group,a CLP group,a dimethyl sulfoxide (DMSO)group and an andrographolide(AND)group.The mice were injected intraperitoneally with 0.2mL normal saline,0.2mL 5% DMSO or 0.2mL andrographolide(10mg/kg)at 1h,6hand 12hafter surgery.The survival rates were assessed 7days after surgery and the survival curve was plotted.Another 48C57BL/6mice were grouped as above.The peripheral blood,peritoneal lavage fluid(PLF),lung and liver tissues were harvested 24hafter operation.Polymorphonuclear leukocyte(PMN)count in PLF was determined.Bacterial loads in the peripheral blood sample and PLF were also determined.The levels of TNF-α,IL-6and IL -10in the blood samples were detected by ELISA.The lung and liver tissues were observed and analyzed by hematoxylin- eosin staining.Results Compared with CLP group,AND group had a significantly increased survival rate 7days after operation (P0.01),a significantly decreased PMN count in PLF (P0.01),a significantly enhanced bacterial clearance capability in both blood and PLF(P0.01),significantly decreased serum TNF-αand IL-6levels,significantly increased IL-10level, and significantly alleviated lung and liver tissue injuries (P0.01).The above parameters were not significantly different between the DMSO group and CLP group.Conclusion Andrographolide has protective effect against CLP-induced sepsis in mice,which might be associated with regulation of the immunological function,enhancement of bacterial clearance and inhibition of excessive inflammatory response during sepsis.

Protective effect of andrographolide against concanavalin A-induced liver injury

This study was designed to investigate the hepatic protective effect and the molecular mechanisms of andrographolide in concanavalin A-induced liver injury model. Results showed that andrographolide (Ag) attenuated concanavalin A (Con-A)-induced liver injury and inhibited hepatocyte apoptosis. Further results showed that oxidative stress response genes were significantly elevated during the pathogenesis induced by Con-A. Meanwhile, gadolinium chloride and N-acetyl-L-cysteine (NAC) treatment, which inactivates Kupffer cells or reduces reactive oxygen species, respectively, prevented the liver injury. So the messenger RNA levels of the oxidative response genes mentioned above were detected, and the following results showed that Ag treatment reduced their expression. Besides, serum lactate dehydrogenase and myeloperoxidase activity was significantly reduced by Ag. Finally, Ag treatment did not further reduce serum tumor necrosis factor-α production compared with NAC treatment alone. Thus, our results indicate that Ag prevents Con-A-induced liver injury and reduced the hepatic oxidative stress response. The hepatic protective effect of Ag indicates that Ag supplementation may be beneficial in the treatment of immune-mediated liver injury.

Antihepatotoxic Activity of Diterpenes ofAndrographis Paniculata(Kal-Megh) AgainstPlasmodium Berghei-InducedHepatic Damage inMastomys Natalensis

AbstractAdministration of an alcohol extract of Andrographis paniculata (25 mg/kg) and two of its constituent diterpenes, andrographolide and neoandrographolide (6 mg/kg/day for two weeks) showed significant antihepatotoxic action in P. berghei K173- induced hepatic damage in M. natalensis. The increased levels of serum lipoprotein-X, alkaline phosphatase, GOT, GPT and bilirubin were markedly reduced by A. paniculata and its diterpenes. In the liver, these preparations decreased the levels of lipid peroxidation products and facilitated the recovery of superoxide dismutase and glycogen. The protective effects of andrographolide were comparable to those of neoandrographolide.