Andrographolide Inhibits Mechanical and Thermal Hyperalgesia in a Rat Model of HIV-Induced Neuropathic Pain

Abstract

Aim: In this study, we investigated whether andrographolide (Andro) can alleviate neuropathic pain induced by HIV gp120 plus ddC treatment and the mechanism of its action.Methods: The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in all groups of the rats, including control group, control combined with Andro treatment group, sham group, gp120 combined with ddC treatment group, gp120 plus ddC combined with A438079 treatment group, and gp120 plus ddC combined with Andro treatment by intrathecally injecting at a dose of 25 μg/20 μl group. The protein expression levels of the P2X7 receptor, tumor necrosis factor-α-receptor (TNFα-R), interleukin-1β (IL-1β), IL-10, phospho-extracellular regulated protein kinases (ERK) (p-ERK) in the L4–L6 dorsal root ganglia (DRG) were measured by western blotting. Real-time quantitative polymerase chain reaction was used to test the mRNA expression level of the P2X7 receptor. Double-labeling immunofluorescence was used to identify the co-localization of the P2X7 receptor with glial fibrillary acidic protein (GFAP) in DRG. Molecular docking was performed to identify whether the Andro interacted perfectly with the rat P2X7 (rP2X7) receptor.Results: Andro attenuated the mechanical and thermal hyperalgesia in gp120+ddC-treated rats and down-regulated the P2X7 receptor mRNA and protein expression in the L4–L6 DRGs of gp120+ddC-treated rats. Additionally, Andro simultaneously decreased the expression of TNFα-R and IL-1β protein, increased the expression of IL-10 protein in L4–L6 DRGs, and inhibited the activation of ERK signaling pathways. Moreover, Andro decreased the co-expression of GFAP and the P2X7 receptor in the SGCs of L4–L6 DRG on 14th day after surgery.Conclusion: Andro decreased the hyperalgesia induced by gp120 plus ddC.

Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L.

“…The inhibitory effect of 78.13 µg/ml HPE was comparable to that of 10 µg/ml ribavirin in vitro , and 480 mg/kg HPE was comparable to that of 60 mg/kg ribavirin in vivo . In the efficacy of antiviral effects, as in the reporting of others herbs (Choi et al, 2016; Sun et al, 2016; Choi et al, 2017; Yi et al, 2018; Luo et al, 2019), the effects of the herbal extract were lower than ribavirin even under several times higher dosage against IBV mRNA level, virus titer, and histopathological injury caused by IBV. However, it is logical since ribavirin is pure compared to the extracts containing many inactive compounds.…”

“…Therefore, the use of traditional antiviral herbs with no obvious side effects on the human body is still a major focus. Some reports have confirmed that traditional Chinese herbs could effectively inhibit the infection and replication of various viruses (Li et al, 2009; Wang et al, 2015; Choi et al, 2016; Sun et al, 2016; Choi et al, 2017; Yin et al, 2017; Yi et al, 2018; Luo et al, 2019). Hypericum perforatum L. belongs to the genus Guttiferae , which contains approximately 400 species all over the world.…”

β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain

“…However, to our knowledge this is the first study to report the expression of Erk1/2 in the CNS after antiretroviral drug treatment. In the periphery, the ratio of p-ERK1/2 to ERK1/2 was increased in the DRG of rats treated with HIV gp120 plus ddC [72]. However, peripheral (intradermal) administration of an Erk1/2 inhibitor was reported to have no effect on ddC-induced mechanical hypersensitivity [11].…”

Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19

“…Moreover, several clinical trials demonstrate its positive effects on infectious disease, autoimmune disorders and it has a potential effect against viral defenses [44,50,52]. Moreover, it exerts anti-viral activity towards a number of different viruses including HIV, hepatitis B, herpes simplex, influenza, hepatitis C, chikungunya virus (CHIKV), Epstein-Barr virus (EBV), human papillomavirus (HPV) dengue virus (DENV) and others [51,56,57,[61][62][63][64][65][66][67][68][69][70][71][72]. Recent studies showed that andrographolide is a potential inhibitor of the main protease of SARS-CoV-2 through in silico studies, such as molecular docking, target analysis, toxicity prediction and ADME prediction (absorption, distribution, metabolism, and excretion) [57].…”