An Update On Proficiency of Voltage-gated Ion Channel Blockers in the Treatment of Inflammation-associated Diseases.

Inflammation is the body's mechanism to trigger the immune system, thereby preventing bacteria and viruses from manifesting their toxic effect. Inflammation plays a vital role in regulating inflammatory mediator levels to initiate the wound healing process depending on the nature of the stimuli. This process occurs due to chemical release from white blood cells by elevating blood flow to the site of action, leading to redness and increased body temperature. Currently, there are numerous Non-steroidal anti-inflammatory drugs (NSAIDs) available, but these drugs are reported with adverse effects such as gastric bleeding, progressive kidney damage, and increased risk of heart attacks when prolonged use. For such instances, alternative options need to be adopted. The introduction of voltage-gated ion channel blockers can be a substantial alternative to mask the side effects of these currently available drugs. Chronic inflammatory disorders such as rheumatoid and osteoarthritis, cancer and migraine, etc., can cause dreadful pain, which is often debilitating for the patient. The underlying mechanism for both acute and chronic inflammation involves various complex receptors, different types of cells, receptors, and proteins. The working of voltage-gated sodium and calcium channels is closely linked to both inflammatory and neuropathic pain. Certain drugs such as carbamazepine and gabapentin, which are ion channel blockers, have greater pharmacotherapeutic activity for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. This review intends to provide brief information on the mechanism of action, latest clinical trials, and applications of these blockers in treating inflammatory conditions.

Emerging Role of Interleukins for the Assessment and Treatment of Liver Diseases.

BACKGROUND: The most common liver diseases are fibrosis, alcoholic liver disease, nonalcoholic fatty disease, viral hepatitis, and hepatocellular carcinoma. These liver diseases account for approximately 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of the worldwide burden. The most widely used liver function tests for diagnosis are alanine transaminase, aspartate transaminase, serum proteins, serum albumin, and serum globulins, whereas antivirals and corticosteroids have been proven to be useful for the treatment of liver diseases. A major disadvantage of these diagnostic measures is the lack of specificity to a particular tissue or cell type, as these enzymes are common to one or more tissues. The major adverse effect of current treatment methods is drug resistance. To overcome these issues, interleukins have been investigated. The balance of these interleukins determines the outcome of an immune response. Interleukins are considered interesting therapeutic targets for the treatment of liver diseases. In this review, we summarize the current state of knowledge regarding interleukins in the diagnosis, treatment, and pathogenesis of different acute and chronic liver diseases. OBJECTIVE: To understand the role of interleukins in the assessment and treatment of different types of liver diseases. METHODS: A literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: Interleukins, Acute Liver Failure, Alcoholic Liver Disease, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, Hepatocellular Carcinoma, Inflammation, Liver injury, Hepatoprotective effect. Clinical trial data on these interleukins have been searched on Clinicaltrials.gov. RESULTS: Existing literature and preclinical and clinical trial data demonstrate that interleukins play a crucial role in the pathogenesis of liver diseases. CONCLUSION: Our findings indicate that IL-1, IL-6, IL-10, IL-17, IL-22, IL-35, and IL-37 are involved in the progression and control of various liver conditions via the regulation of cell signaling pathways. However, further investigation on the involvement of these interleukins is necessary for their use as a targeted therapy in liver diseases.

Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation.

Inflammation is not only a defense mechanism of the innate immune system against invaders, but it is also involved in the pathogenesis of many diseases such as atherosclerosis, thrombosis, diabetes, epilepsy, and many neurodegenerative disorders. The World Health Organization (WHO) reports worldwide estimates of people (9.6% in males and 18.0% in females) aged over 60 years, suffering from symptomatic osteoarthritis, and around 339 million suffering from asthma. Other chronic inflammatory diseases, such as ulcerative colitis and Crohn's disease are also highly prevalent. The existing anti-inflammatory agents, both non-steroidal and steroidal, are highly effective; however, their prolonged use is marred by the severity of associated side effects. A holistic approach to ensure patient compliance requires understanding the pathophysiology of inflammation and exploring new targets for drug development. In this regard, various intracellular cell signaling pathways and their signaling molecules have been identified to be associated with inflammation. Therefore, chemical inhibitors of these pathways may be potential candidates for novel anti-inflammatory drug approaches. This review focuses on the anti-inflammatory effect of these inhibitors (for JAK/STAT, MAPK, and mTOR pathways) describing their mechanism of action through literature search, current patents, and molecules under clinical trials.

A Review on Molecular Mechanisms and Patents of Marine-derived Anti-thrombotic Agents.

Thrombosis is a condition of major concern worldwide as it is associated with life-threatening diseases related to the cardiovascular system. The condition affects 1 in 1000 adults annually, whereas 1 in 4 dies due to thrombosis, and this increases as the age group increases. The major outcomes are considered to be a recurrence, bleeding due to commercially available anti-coagulants, and deaths. The side effects associated with available anti-thrombotic drugs are a point of concern. Therefore, it is necessary to discover and develop an improvised benefit-risk profile drug, therefore, in search of alternative therapy for the treatment of thrombosis, marine sources have been used as promising treatment agents. They have shown the presence of sulfated fucans/galactans, fibrinolytic proteases, diterpenes, glycosaminoglycan, glycoside, peptides, amino acids, sterols, polysaccharides, polyphenols, vitamins, and minerals. Out of these marine sources, many chemicals were found to have anti-thrombotic activities. This review focuses on the recent discovery of anti-thrombotic agents obtained from marine algae, sponges, mussels, and sea cucumber, along with their mechanism of action and patents on its extraction process, preparation methods, and their applications. Further, the article concludes with the author's insight related to marine drugs, which have a promising future.

Recent Patents and Discovery of Anti-inflammatory Agents from Marine Source.

BACKGROUND: Inflammation has become pathology in the majority of the prevalent diseases such as diabetes, atherosclerosis, epilepsy and neurodegenerative disorders. Anti-inflammatory drugs work wonder in all these conditions, where the patient has become refractory to standard treatment. However, available anti-inflammatory agents have side effects associated with chronic use, thus if we could develop safe and efficacious molecules, quality of health care provided will improve. Since plant sources have been extensively explored, the focus needs to be shifted on the alternative natural sources of anti-inflammatory agents. Water bodies especially the sea and ocean are under investigation to find agents which can tackle inflammation. OBJECTIVE: This article reviews anti-inflammatory agents obtained from five types of marine organisms namely microalgae, sea cucumber, mussels, sponges and corals. METHODS: A literature search was conducted using PubMed/Science Direct with keywords marine organisms, inflammation, marine sponges, sea cucumber, mussels, corals and microalgae. Patents were searched using the key terms inflammation, marine agents from www.google.com/patents, www.uspto.gov, http://espacenet.com, www.freepatentsonline.com, www.wipo.int/pctdb/en/searchsimp. jsp and www.freshpatents.com. RESULTS: Literature and current patents have revealed applications of anti-inflammatory agents from marine organisms in pharmaceuticals and cosmeceuticals. These agents are used to treat inflammatory disorders ranging from minor allergy to chronic conditions like rheumatoid arthritis. Marine waste is also a valuable resource for nutraceuticals and anti-inflammatory agents. CONCLUSION: The findings reveal that marine organisms could be a promising source of novel antiinflammatory agents. However, further investigations are suggested for the isolation and identification of bioactive, exploring the mechanism of action and evaluating the efficacy in various inflammatory conditions.