Evaluation of the effect of andrographolide and methotrexate combined therapy in complete Freundʼs adjuvant induced arthritis with reduced hepatotoxicity

Li, Fenfen; Li, He; Luo, Shasha; Ran, Yantao; Xie, Xiaoqian; Wang, Yale; Zheng, Ming; Wang, Mengzhen; Zhao, Zeyue; Li, Xiaotian

doi:10.1016/j.biopha.2018.07.001

Cited by 33 publications

(14 citation statements)

References 40 publications

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“…The study revealed that CFA injection induced redness and swelling in the paws, as evidenced by signi cant elevation in paw volume (P ≤ 0.001). This was in agreement with Li et al [16] who reported signi cant elevation of paw volume (P < 0.05) following CFA injection.…”

Section: Discussionsupporting

confidence: 93%

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA like Adjuvant Arthritis in Rats.

Elbeialy

2022

Preprint

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Objective: Nanomedicine has become one of the promising research areas, opening new horizons in disease diagnosis and treatment. Recent years have witnessed a surge in the development of nanomedicine for combating rheumatoid arthritis (RA), the most common autoimmune arthritis. RA is characterized by progressive inflammation and persistent synovitis, leading to joint destruction, functional incapability, and ultimately disability. Although there has been a tremendous evolution in disease assessment and treatment, many patients still fail to attain remission. Therefore, developing new drugs that specifically target inflamed joints and simultaneously attenuate other possible damages to healthy tissues is indispensable. This study was done to evaluate the potential of folic acid conjugated silver nanoparticles (FA-AgNPs) as RA therapy.Methods: In the CFA-arthritic rat model, FA-AgNPs & methotrexate were administered for 8 consecutive weeks. Therapeutic efficacy was evaluated by measuring paw volume, ESR, CRP, TNF-α, and IL-6 levels. For safety concerns, CBC, liver, and renal function tests were evaluated. Joints histological assessment was also carried out.Results: FA-AgNPs significantly reduced paw volume, paw weight, ESR, CRP, RF, TNF-α, and IL-6 levels compared with arthritic non-treated rats, demonstrating good anti-inflammatory activity. Likewise, histology of tarsal joints depicted comparatively lesser inflammatory cellular infiltration and diminished cartilage erosions. Methotrexate displayed comparable results. In contrast to methotrexate, FA-AgNPs showed normal CBC & significantly improved liver and renal function tests. Conclusion: FA-AgNPs exhibited substantial anti-arthritic activity. This notable anti-arthritic potential of FA-AgNPs was as good as the current standard treatment of MTX with higher biosafety.

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Section: Discussionsupporting

confidence: 93%

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA like Adjuvant Arthritis in Rats.

Elbeialy

2022

Preprint

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“…Cobbina E et al found that the presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors in NAFLD (47). Chen HW et al (48) and Li F et al (49) found AG inhibit IL-1, IL-6 and TNF-α-induced inflammation in vivo and in vitro disease models. In their study, pro-inflammatory factors was the evaluation index of inflammation -induced disease and the key therapeutic target for AG.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Shi

et al. 2020

Preprint

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Mechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.Importance HFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

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“…Dysgeusia could be attributed to andrographolide bitterness [31]. Other adverse events described in the literature include constipation, nausea, vomiting, diarrhoea, unpleasant sensations in the chest and intensified headache, although with very low rates of presentation [10,32].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial

et al. 2020

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Background: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been reorganized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. Methods: A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. Results: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was − 0.679% for the AP group and − 1.069% for the placebo group (mean difference:-0.39; 95% CI [− 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was − 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. Conclusions: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. Trial registration: ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.

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Evaluation of the effect of andrographolide and methotrexate combined therapy in complete Freundʼs adjuvant induced arthritis with reduced hepatotoxicity

Cited by 33 publications

References 40 publications

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA like Adjuvant Arthritis in Rats.

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA like Adjuvant Arthritis in Rats.

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial

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