Evaluation of the Hypoglycemic Activity of Morchella conica by Targeting Protein Tyrosine Phosphatase 1B

Abstract

Morchella conica (M. conica) Pers. is one of six wild edible mushrooms that are widely used by Asian and European countries for their nutritional value. The present study assessed the anti-diabetic potential of M. conica methanolic extract (100 mg/kg body weight) on streptozotocin (STZ)-induced diabetic mice. STZ was used in a single dose of 65 mg/kg to establish diabetic models. Body weights, water/food intake and fasting blood glucose levels were measured. Histopathological analysis of the pancreas and liver were performed to evaluate STZ-induced tissue injuries. In addition, in vitro assays such as α-amylase and protein tyrosine phosphatase 1B (PTP1B) inhibitory, antiglycation, antioxidant and cytotoxicity were performed. The in vitro study indicated potent PTP1B inhibitory potential of M. conica with an IC50 value of 26.5 μg/ml as compared to the positive control, oleanolic acid (IC50 36.2 μg/ml). In vivo investigation showed a gradual decrease in blood sugar level in M. conica-treated mice (132 mg/dl) at a concentration of 100 mg/kg as compared to diabetic mice (346 mg/dl). The extract positively improved liver and kidney damages as were shown by their serum glutamic pyruvic transaminase, serum glutamic oxaloacetate, alkaline phosphatase, serum creatinine and urea levels. Histopathological analysis revealed slight liver and pancreas improvement of mice treated with extract. Cytotoxicity assays displayed lower IC50 values. Based on the present results of the study, it may be inferred that M. conica are rich in bioactive compounds responsible for antidiabetic activity and this mushroom may be a potential source of antidiabetic drug. However, further studies are required in terms of isolation of bioactive compounds to validate the observed results.

Update on potential of edible mushrooms: high‐value compounds, extraction strategies and bioactive properties

“…The properties and biological activities associated with mushrooms here summarised could have a potential interest in several industries belonging to pharmaceutic or/and nutraceutical fields. In order to advance in the application of mushroom bioactives in the formulation of novel foods, further work is required in relation to the adoption of a holistic approach for mushroom utilisation in functional food (Mingyi et al, 2019); to the definition of the particular bioactive compounds in mushrooms, enabling that the findings be adopted into clinical practice and replication of studies in different population groups (Blumfield et al, 2020); or in vivo studies to determine the appropriate doses, side effects and action spectrum of different bioactive compounds and fractions (Tan et al, 2021).…”

“…On this basis, mushrooms could be considered as potential novel antitumour agents although these resources also showed other potential valuable medicinal uses. For instance, Morchella conica methanolic extract provided antidiabetic effects since the oral treatment of streptozotocin‐induced diabetic mice concluded into the reduction of blood glucose levels and hyperglycaemic index, with minimal histopathologic and necrotic modifications in liver and pancreas tissues (Begum et al ., 2021). Ethanolic extracts from Ganoderma cochlear and G. lucidum were also appropriate to enhance insulin resistance and renal fibrosis diseases due to the healthy action of meroterpenoids (Qin et al, 2021).…”

“…Mushrooms have been reported to possess hypocholesterolaemia, antimicrobial, antioxidant, hepatoprotective, cardiometabolic regulator, immunomodulatory, antitumoral, neuroprotective, prebiotic and antiobesity effects (Gait an-Hern andez et al, 2019;Kumar, 2020;Tan et al, 2021). In addition to some recent reviews focused on the biological properties of particular species (Gait an-Hern andez et al, 2019;Blumfield et al, 2020;Kumar, 2020;Lin et al, 2020), abundant studies on mushroom polysaccharides can be found (Mingyi et al, 2019;Yin et al, 2020;Wang et al, 2022), and recent discoveries, new extraction techniques and bioactivities have been updated (Rodrigues Barbosa et al, 2020). Overall, mushrooms can be an excellent low-cost source of good quality proteins alternative to those of animal origin, but maintaining essential amino acids (Kumar, 2020).…”

Distribution of edible, toxic and medicinal wild mushrooms in Europe and Bulgaria

“…Morchella conica Pers. is one of six wild edible mushrooms that are widely used in Europe and Asisa not only for their nutritional value but also as a potential source of antidiabetic drugs [36].…”

Allosteric Inhibition of PTP1B by a Nonpolar Terpenoid

“…These enzymes regulate cellular growth, motility, and oncogenic transformation, and contribute to a broad set of complex physiological processes (e.g., memory, inflammation, metabolism, and autoimmunity). [1][2][3][4][5][6][7][8] Classical PTPs catalyze the hydrolytic dephosphorylation of tyrosine residues with four conserved active site loops: (i) the P-loop (C(X)5R(S/T)), where an arginine facilitates substrate binding and transition state stabilization and a cysteine enables nucleophilic attack of the phosphate ester, (ii) the WPD loop (10-12 residues), which has the general acid catalyst required for hydrolysis, (iii) the Q-loop, where a glutamine positions a water for nucleophilic attack of the phosphocysteine intermediate, and (iv) the substrate binding loop, which selects for phosphorylated tyrosine residues. 9 The conserved active site of PTPs has hindered the design of selective therapeutics.…”