Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5367_Библиотеки_им_академика_М_И_Перельмана

Monoamine oxidase is widely distributed in the periphery as well as the CNS and is involved in the metabolism of various monoamines. It is present in two isoforms, namely MAO-A and MAO-B. 5-HT, norepinephrine and dopamine have specic selectivity with MAO-A, which is the key enzyme for their metabolism (Myburg et al, 2022). Numerous preclinical and clinical studies suggested increased expres­sions of MAO in chronic stress-induced rats and depressed patients (Domschke et al, 2008; Stefanovic et al, 2016). It was found that under the stress conditions activa­tion of kruppel-like factor 11 upregulates the MAO-A activity, which further rapidly breaks down the monoamines such as 5-HT and dopamine resulting in MDD (Harris et al, 2015). A number of phytoconstituents have been evaluated and reported as MAO-A inhibitors which attenuate depression-like behaviour in rats. Plants like SJW, with active constituent hypericin which is an MAO-A inhibitor, have been used from ancient times to treat MDD (Assadi et al, 2011; Suzuki et al, 1984). Many polyherbal formulations contain phytoconstituents such as harmine (Peganum har- mala L.), punarnavine (Boerhaavia diffusa L.) (Dhingra and Valecha, 2014) hyper­forin and adhyforin (Hypericum perforatum L.) act via modulation of MAO activity (Jensen et al, 2001). Curcuma longa L. contain active phytoconstituents curcumin A and curcumin B. In vitro study of the MAO-A activity showed that curcumin A possess inhibitory effect on it with a docking score of −9.78 kcal/mol by in silico molecular simulation method (Aswar et al, 2020; Nazemi et al, 2019). Further in silico and in vivo evaluation by isolation of ethanolic extract of Piper longum L. a piperine alkaloid and its derivative antiepilepsirine showed antidepressant effect. Piperine competitively inhibits MAO-A with Ki 19.0 ± 0.9 μM. The antidepressant activity was further conrmed by reduced immobility in tail suspension and force swim tests (Li et al, 2007). Another preclinical study in CUMS model in mice where administration of water extract of Gastrodia elata Blume (0.5 mg/kg) and palmatine (0.5 mg/kg) has shown to reduce the MAO-A and increased 5-HT in the hippocam­pus. It was supported by behavioural study, sucrose preference test and open eld test (Dhingra and Bhankher, 2014).

2013). Another phytoconstituent salidroside present in Rhodiola rosea was studied in olfactory bulbectomy- induced rats. Administration of salidroside (20, 40 mg/kg p.o) for 2 weeks remarkably reduced the tumour necrosis factor-alpha (TNF-α) and IL-1 beta (IL-1β) levels and markedly increased the GC expression in the hip- pocampus. Salidroside showed its antidepressant effect by reduction of CRH in thehypothalamus and serum cortisol levels (Yang et al, 2014). Phytoconstituents are multifunctional in nature which not only target a single disease but also attenuate the comorbidities associated with it. Depression associated with diabetes worsens the diabetic symptoms and blood glucose. The activation of inammatory mediators leads to HPA axis activation and oxidative stress, thus making diabetes depression a vicious cycle (Patil and Aswar, 2021). A potent avonoid quercetin is richly present in apples, broccoli and ginkgo biloba. In a preclinical study on diabetic depressed rats when administered (100 mg/kg i.p.), balanced the HPA axis and reduced blood glucose levels (Demir et al, 2016). The important and key regulator for neuroin­ammation associated with depression is nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) which regulates TNF-α, IL-6, IL-1 and IL-10 levels. Due to its direct correlation with depression, various polyphenols were studied for its inhibitory activity. The polyphenols are ferulic acid, chrysin and hesperi­din (Borges Filho et al, 2016; Zheng et al, 2019). It was found that stress activates the glycogen synthase kinase-3 beta (GSK3β) which further stimulates inamma­tory cascade by increasing NF-κB activity leading to the activation of nucleotide­binding domain, leucine-rich–containing family, pyrin domain–containing-3 inammasome (NLRP-3). They also stimulate caspase 1 activity which helps in the formation of immature to mature form of IL-1β in the hippocampus. Baicalin a polyphenol obtained from the Scutellaria baicalensis Georgi, phosphorylate the GSK3β and further activate NF-κB. Baicalin attenuates depressive symptoms by

The catalepsy caused by haloperidol and the stereotypy caused by amphetamine can both be re duced by methanolic preparat ions of Vitex negundo L. roots. DA-induced contractions of the vas deferens can also be suppressed. Its anti-dopaminergic action was demonstrated by this research. The neuroprotective compounds found in Vitex negundo are called vitegnoside, negundoside, agunside, avones, luteolin and cas­ticin. However, further in-depth research is needed to determine the phytochemi­cal that gives Vitex negundo its anti-psychotic properties. The dopamine theory of psychosis is currently out of date because recent research has shown that psychosis involves more than only the D2 receptor. Targets for innovative medication include the function of 5-HT (1 and 2A) receptors and glutamate receptors with D2 antago­nism. Similarly, the plants/phytochemicals used by traditional healers are known to act with myriad effects on different receptors, neurotransmitters and channels as well. Cannabis sativa contains an alkaloid known as the cannabinoid. According to research, it is the rst clinical experiment to examine potential antipsychotic effects of CBD. Nineteen patients received 800 mg of CBD as monotherapy for 4 weeks, and the impact on the PANSS and BPRS was examined. The effects of CBD were found to be equivalent to amisulpride, the standard treatment; moreover, CBD was devoid of any extrapyramidal side effects as observed with amisulpride. Many more clinical trials were conducted in later years and suggested the antipsychotic effect of CBD at a dose ranging from 800 to 1000 mg for 4 weeks. CBD is known to act via 5HT1A receptor and GPR55 (novel cannabinoid receptor) activation. The GPR55 is present abundantly in CNS, its activation improves psychotic symptoms and cogni­tive impairments, as well as neuroinammation (Dyck et al, 2021). Caryophyllene, obtained from the same plant, is also demonstrated to prevent positive and negative symptoms in patients at a dose of 0.4 mg/kg to about 2 mg/kg by acting cannabinoid receptor type 2 receptors (Anavi-Goffer et al, 2016). Stephalidine (SPD) is another important constituent of Chinese herbal medicine Stephania intermedia. SPD is found to exhibit a D2 antagonism effect while having D1 agonistic activity. It stimu­lated apomorphine (specic D1) induced rotations while inhibiting amphetamine (specic D2) induced rotations in the 6-OHDA model. Dual actions of (-)-stepholidine on dopamine receptor subtypes after substantia nigra lesion. Moreover, it inhibited prepulse inhibition and increased the hindlimb retraction time indicating its D2 antagonistic effect thereby exhibiting an antipsychotic effect with low potency to induce EPS (Ellenbroek et al, 2006). Baicalin is a polyphenol present in plants such as Scutellaria baicalensis, found to alleviate the negative symptoms associated with SZ when given as an adjunct to olanzapine. The study was carried out on 45 patients, and the treatment was given for 24 weeks. The treatment attenuated PANSS scores