Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood–brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-β1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70–80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, β-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

BRIC basically include the emerging markets of Brazil, Russia, India and China. The growth of pharmaceutical market in these countries has been very eye-popping during the last two decades. The growth of pharmaceutical market depends upon the drug regulatory system and drug regulatory laws. The drug regulatory system in these countries is on the way of continuous improvement e.g. introduction of product patent in India, provisions for drug approval in China, bioequivalence testing requirement in Brazil, Russian new law on circulation of medicines 2010. In this article the drug regulatory system of BRIC countries has been analyzed. These drug regulatory trends include following: drug regulatory framework, drug regulatory laws, clinical trials, drug registration procedures, drug pricing mechanism, GMP practices, pharmacovigilance, patents system on pharmaceuticals, patent linkage and data protection, etc. Drug regulatory framework has been analyzed by studying the composition of various central and state drug regulatory authorities and drug testing institutions regulating the pharmaceutical industry. The basic drug regulatory laws regulating approval, manufacturing, packing, labeling, selling, advertising, use of drugs, cosmetics and medical devices has been reported. The drug pricing mechanism over the essential and nonessential drugs and drug price calculation formula has been reported. The drug manufacturing law, manufacturing approval and inspection system has also been analyzed. The pharmacovigilance system for the reporting of Adverse Drug Reactions in these countries has been studied. Finally an analysis of the intellectual property rights related to pharmaceuticals has been made in BRIC countries.

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: Rheumatoid arthritis is an auto-immune disorder, recognized by cartilage as well as bone destruction which causes irreversible joint deformities, which further results in functional limitations in the patient. Genes like HLA-DRB1 and PTPN22 are likely implicated in the genetic predisposition of rheumatoid arthritis pathology. The first and foremost clinical manifestation person with rheumatoid arthritis, is joint destruction followed by cartilage and bone destruction caused by cell-cell interactions. The cell-cell interactions are thought to be initialized through the contact of Antigenpresenting cell (APC) with CD4+ cells, all this leads to the progression of the disease. APC includes a complex of class ІІ major histocompatibility complex molecules along with peptide antigens and binds to the receptors present on the surface of T-cells. Further, the activation of macrophage is followed by the release of various pro-inflammatory cytokines such as IL-1 and TNF-α which leads to the secretion of enzymes that degrade proteoglycan and collagen which in turn increases the tissue degradation. Biomarkers like IL-6, IL-12, IL-8 and IL-18, 14-3-3η, RANKL, IFN-γ, IFN-β and TGF-β have been designated as key biomarkers in disease development and progression. The study of these biomarkers is very important as it acts as a molecular indicator of pathological processes that aggravate the disease.