Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats.

Liquiritigenin (LTG) and its bioprecursor isoliquiritigenin(ISL), the main bioactives from roots of Glycyrrhiza genus are progressively documented as a potential pharmacological agent for the management of chronic diseases. The aim of this study was to evaluate the pharmacological potential of liquiritigenin, isoliquiritigenin rich extract of Glycyrrhiza glabra roots (IVT-21) against the production of pro-inflammatory cytokines from activated macrophages as well as further validated the efficacy in collagen-induced arthritis model in rats. We also performed the safety profile of IVT-21 using standard in-vitro and in-vivo assays. Results of this study revealed that the treatment of IVT-21 and its major bioactives (LTG, ISL) was able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-activated primary peritoneal macrophages in a dose-dependent manner compared with vehicle-alone treated cells without any cytotoxic effect on macrophages. In-vivo efficacy profile against collagen-induced arthritis in Rats revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in serum. IVT-21 oral treatment is also able to reduce the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue and mRNA level of pro-inflammatory cytokines in paw tissue in a dose-dependent manner when compared with vehicle treated rats. Acute oral toxicity profile of IVT-21 demonstrated that it is safe up to 2000 mg/kg body weight in experimental mice. This result suggests the suitability of IVT-21 for further study in the management of arthritis and related complications.

Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neuro-motor ailment that strikes adults in their older life and results in both motor and non-motor impairments. In neuronal and glial cells, PD has recently been linked to a dysregulated autophagic system and cerebral inflammation. Chloroquine (CQ), an anti-malarial drug, has been demonstrated to suppress autophagy in a variety of diseases, including cerebral ischemia, Alzheimer's disease (AD), and Traumatic brain injury (TBI), while its involvement in PD is still unclear. BALB/c mice were randomly allocated to one of four groups: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), CQ treatment with or without MPTP, or control. The CQ treatment group received CQ (intraperitoneally, 8 mg/kg body weight) after 1 h of MPTP induction on day 1, and it lasted for 7 days. CQ therapy preserves dopamine levels stable, inhibits tyrosine hydroxylase (TH) positive dopaminergic cell death, and lowers oxidative stress. CQ reduces the behavioural, motor, and cognitive deficits caused by MPTP after injury. Furthermore, CQ therapy slowed aberrant neuronal autophagy (microtubule-associated protein-1 light chain 3B; LC3B & Beclin1) and lowered expression levels of the inflammatory cytokines interleukin 1 (IL-1ß) and tumour necrosis factor (TNF-α) in the mice brain. In addition, CQ's antioxidant and anti-inflammatory effects were also tested in MPTP-mediated cell death in PC12 cells, demonstrating that CQ has a neurorestorative impact by successfully rescuing MPTP-induced ROS generation and cell loss. Our findings show that CQ's can help to prevent dopaminergic degeneration and improve neurological function after MPTP intoxication by lowering the harmful effects of neuronal autophagy and cerebral inflammation.