Role of Acetylcholine in Chronic Diseases

The complex and extensive network of brain signals plays a vital role in maintaining physiological mechanisms and homeostasis. Acetylcholine, a chief neurotransmitter of the parasympathetic nervous system, is an important component of the cholinergic system along with cholinergic receptors, acetylcholinesterase, and choline acetyltransferase. It is responsible for mediating cell-to-cell communication and regulates various peripheral and non-neuronal cholinergic signals. Any alteration in the levels of acetylcholine leads to chronic diseases. Chronic diseases, the leading causes of disability, require continuing health care, medical attention, and potential therapeutics. This chapter will cover a brief overview of acetylcholine including its synthesis and degradation, the cholinergic system, and the influence of acetylcholine on different chronic diseases including neurological complications, metabolic disorders, cardiac diseases, and immune disorders. Moreover, the mechanistic approach of acetylcholine in different diseases and the therapies for recovering the levels of acetylcholine will be reviewed in this chapter. Further, this will illustrate the acetylcholine interaction with various cells implicated in the diseases. The insights on agonists and antagonists of acetylcholine and different targets of cholinergic receptors that could help to design better strategies to control these chronic diseases will also be provided

Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models

Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications