Biochemical and toxicity evaluation of Retama sphaerocarpa extracts and in-silico investigation of phenolic compounds as potential inhibitors against HPV16 E6 oncoprotein.

Cervical cancer is a type of cancer which affects the cervix cells. The conventional treatments for cervical cancer including surgery, chemotherapy, and radiotherapy are only effective in premature stages and less effective in late stages of this tumor. Therefore, the therapeutic strategies based on biologically active substances from plants are needed to develop for the treatment of cervical cancer. The aim of the present study was to assess in vivo toxicity, hematological and biochemical blood parameters in Wistar rats fed Retama sphaerocarpa aqueous leaf extract (RS-AE), as well as to perform in silico molecular docking studies and dynamic simulation of phenolic compounds against HPV16 oncoprotein E6 in order to identify potential inhibitors. RS-AE was found not to induce acute or sub-acute oral toxicity or significant alterations in hematological and biochemical blood parameters in Wistar rats. A total of 11 phenolic compounds were identified in RS-AE, including dihydrodaidzein glucuronide, chrysoperiol pentoside, genistin and vitexin, which turned out to have the highest binding affinity to HPV16 oncoprotein E6. Based on these results, these RS-AE phenolic compounds could be used as natural drugs against the HPV16 E6 oncoprotein.

Antihypertensive and ACE-2 Inhibitory Effects of Daphne gnidium in Rats.

AIMS: The antihypertensive activity of Daphne gnidium was tested. BACKGROUND: Daphne gnidium (Thymelaeaceae) is used against hypertension. OBJECTIVE: The antihypertensive effect of Daphne gnidium was evaluated in this study. METHODS: The effect of Daphne gnidium aqueous extract (DGAE, 100 and 180 mg/kg) on blood pressure was evaluated in rats. In addition, the vasorelaxant effect of this extract was also tested. RESULTS: DGAE lowered blood pressure in hypertensive rats and exhibited vasorelaxant activity. In addition, cumulative concentrations of DGAE induced vasodilatation through receptoractivated calcium channels (ROCCs) without affecting ACE-2. CONCLUSION: The aqueous extract of Daphne gnidium exhibits antihypertensive activity and induces vasodilatation via the inhibition of Ca2+ entry.

Antidiabetic and Antidyslipidemic Effects of Artemisia mesatlantica, an Endemic Plant from Morocco.

AIMS: The study aimed to assess the antihyperglycemic and antidyslipidemic activities of Artemisia mesatlantica. BACKGROUND: Artemisia mesatlantica is an endemic plant of Morocco used in traditional medicine as an alternative treatment for diabetes. OBJECTIVE: The study was designed to examine the antihyperglycemic and antidyslipidemicability of aqueous extract of Artemisia mesatlantica (AMAE) in experimental animal models. METHODS: The effect of the single and repeated oral administration (7 days of treatment) of AMAE (60 mg/kg) on blood glucose and lipid profile were assessed in normal and streptozotocin-induced diabetic rats. Furthermore, to confirm the antidyslipidemic effect of Artemisia mesatlantica, a model of hyperlipidemia induced by tyloxapol (Triton WR-1339) in rats was used. RESULTS: The AMAE (60 mg/kg) was able to significantly reduce glycaemia, improve lipid profile and increase hepatic glycogen content in STZ-induced diabetic rats. In addition, pretreatment of rats for 7 consecutive days with an aqueous extract of Artemisia mesatlantica (600 mg/kg) prior to tyloxapol injection prevented increases in plasma levels of total cholesterol, triglycerides and LDL-c. CONCLUSION: From these observed results, it can be deduced that Artemisia mesatlantica possesses remarkable antidiabetic and antihyperlipidemic properties.

L-Tartaric Acid Inhibits Diminazene-induced Vasorelaxation in Isolated Rat Aorta.

AIMS: The study investigated the effect of L-tartaric acid on diminazene-indiuced vasorelaxation. BACKGROUND: Diminazene is known to induce vasorelaxation through the stimulation of angiotensin-converting enzyme (ACE-2). OBJECTIVE: This work was designed to study the effect of L-tartaric acid on diminazene-induced vasorelaxation using an ex vivo approach. MATERIAL AND METHODS: In the current investigation, the inhibitory effect of L-tartaric acid on diminazene-induced relaxation. RESULTS: The results confirmed that L-tartaric acid was able to inhibit in a dose-dependent manner diminazene-induced vasorelaxation. CONCLUSION: This investigation provides important experimental evidence of the efficacy of L-tartaric acid in inhibiting diminazene-induced vasorelaxation.

L-Tartaric Acid Exhibits Antihypertensive and Vasorelaxant Effects: The Possible Role of eNOS/NO/cGMP Pathways.

AIMS: The aim of the study was to investigate the antihypertensive effect of L-Tartaric acid. BACKGROUND: L-Tartaric acid (L-TA) is a well-known weak organic acid that naturally occurs in a wide range of fruits, most notably in grapes, tamarind, and citrus. OBJECTIVE: The present study aimed to assess the effect of acute and subchronic administration of L-TA on blood pressure parameters in normotensive and hypertensive rats as well as its vasorelaxant potency. METHODS: In the current study, the antihypertensive activity of L-TA was pharmacologically studied. L-NAME-induced hypertensive and normotensive rats received L-TA (80 and 240 mg/kg) orally over six hours for the acute experiment and seven days for the subchronic treatment. Thereafter, systolic, diastolic, mean, mid arterial blood pressure, and pulse pressure as well as heart rate were evaluated. In the in vitro experiment, the vasorelaxant ability of L-TA was performed in ratisolated thoracic aorta. RESULTS: An important drop in blood pressure was recorded in L-NAME-induced hypertensives treated with L-TA. This molecule also produced a dose-dependent relaxation of the aorta precontracted with norepinephrine (NEP) and KCl. The study demonstrated that the vasorelaxant capacity of L-TA seems to be exerted through the activation of eNOS/NO/cGMP pathways.

Study of the Antihypertensive Effect of Laurus nobilis in Rats.

AIMS: The study aimed to study the antihypertensive activity of Laurus nobilis. BACKGROUND: Laurus nobilis L. is used to treat hypertension in Morocco. OBJECTIVE: The study was designed to investigate the effect of the aqueous extract leaves of Laurus nobilis (AELN) on blood pressure. MATERIALS AND METHODS: The antihypertensive and vasorelaxant activities of AELN were pharmacologically investigated in normotensive and L-NAME-induced hypertensive rats. Thereafter, blood pressure was evaluated, and the ex-vivo vasorelaxant activity of this extract was performed. RESULTS: A considerable decrease in blood pressure parameters were observed in L-NAMEinduced hypertensive rats treated with AELN. The extract induced a vasorelaxant effect on the aorta precontracted with epinephrine or KCl by inhibiting extracellular Ca2+ entry. CONCLUSION: The study demonstrates that Laurus nobilis aqueous extract exhibits potent antihypertensive and vasorelaxant activities via inhibiting Ca2+ entry.

Antihypertensive Activity of Prunus armeniaca in Hypertensive Rats.

AIMS: The goal of this work was to evaluate the antihypertensive activity of Prunus armeniaca. BACKGROUND: Prunus armeniaca is known for its beneficial medicinal properties. OBJECTIVE: This study aimed to evaluate the effect of the aqueous extract of Prunus armeniaca L. (P. armeniaca) leaves (PAAE) on arterial blood pressure in normotensive and hypertensive rats. MATERIALS AND METHODS: In the in vivo examination, N-omega-Nitro-L-arginine methyl ester hydrochloride( L-NAME)-induced hypertensive and normotensive rats received PAAE (160 and 100 mg/kg) orally for the acute experiment spanning 6 hours and for seven days for the subchronic treatment; their blood pressure parameters were also evaluated. In the in vitro experiment, isolated intact thoracic aortic rings were precontracted with KCl (80 mM) and epinephrine (EP) (10 µM), and vascular dilatation was assessed. RESULTS: PAAE lowered blood pressure parameters in L-NAME-induced hypertensive without affecting normotensive rats following oral administration, suggesting that PAAE possesses an antihypertensive effect. In addition, PAAE (0.25-1 mg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted by EP (10 µM), and this effect was especially reduced in the presence of glibenclamide or nifedipine. However, PAAE (0.25-1 mg/mL) had only a minimal vasorelaxant effect on thoracic aortic rings precontracted by KCl (80 mM). CONCLUSION: The results demonstrate that the P. armeniaca aqueous extract possesses potent antihypertensive and vasorelaxant activity, and its vasorelaxant activity seems to be mediated through the opening of ATP-sensitive K+ channels and inhibition of L-type calcium channels.

In silico Evaluation of ACE2 Inhibition by Prunus armeniaca L. and in vivo Toxicity Study.

BACKGROUND: SARS-CoV-2 is a virus that uses ACE2 to enter the host cell. AIMS AND OBJECTIVES: This study aimed to evaluate the in silico inhibitory activity of polyphenols from Prunus armeniaca (P. armeniaca) on angiotensin-converting enzyme 2 (ACE2). METHODS: The efficacy of phytocompounds from P. armeniaca in inhibiting ACE2 was tested through molecular docking and dynamic analyses. The toxicological analysis of P. armeniaca was also evaluated. RESULTS: A total of twenty polyphenols were docked against the ACE2 active site, and four compounds showed interesting profiles. In vivo acute toxicity study demonstrated that the aqueous extract of Prunus armeniaca was safe. CONCLUSION: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.

Antihyperglycemic effect of aqueous extract of Tetraclinis articulata in streptozotocin-induced diabetic rats and acute toxicity analysis.

AIMS: The study aimed to evaluate the glucose-lowering effect of Tetraclinis articulata. BACKGROUND: Tetraclinis articulata is commonly used for the treatment of diabetes characterized by chronic hyperglycemia. OBJECTIVE: This work aimed to evaluate the effect of Tetraclinis articulata (T. articulata) aqueous extract (TAAE) on glycaemia and lipid profile in normal and streptozotocin(STZ)-induced diabetic rats. Additionally, its acute toxicity, phytochemical composition, and antioxidant capacity were assessed. METHODS: To highlight the effect of TAAE on plasma glucose levels and lipid metabolism, blood glucose levels were measured at 1, 2, 4, and 6 hours of treatment for the acute test and on days 2, 4 and 7 over the daily oral administration for the subchronic test at two selected doses (10 mg/kg and 20 mg/kg). Furthermore, Triglycerides (TGs), total cholesterol (TC), and High-density lipoprotein cholesterol (HDL-c) were measured after the treatment. The rats' liver, extensor digitorum longus (EDL), and soleus muscle were isolated from diabetic rats treated with TAAE at a dose of 20 mg/kg at the end of the experiment to measure glycogen content using a standard method. The acute toxicity of TAAE was examined according to the OECD guideline. In addition, body weight, signs of toxicity, and/or mortality were observed for 14 days. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity were evaluated. RESULTS: The results showed that TAAE at the doses of 10 and 20 mg/kg possesses a potent antihyperglycemic effect in STZ-treated diabetic rats and an acute hypoglycemic effect in normal rats, as well as, the extract provoked a decrease of blood glucose levels after glucose loading in the glucose tolerance test in a dose-dependent manner. TAAE at a dose of 20 mg/kg revealed a significant improvement of the lipid profile. However, treatment with TAAE at a dose of 20 mg/kg did not significantly modify the glycogen content. In the same way, the acute toxicity analysis revealed no death or signs of toxicity in rats, and the LD50 value was more than 2 g/kg. In addition, preliminary phytochemical screening revealed that TAAE revealed the presence of polyphenols, flavonoids, tannins, carbohydrates, saponins, quinones, sterols and terpenoids. Furthermore, TAAE exhibited a potent antioxidant activity which may be due to the richness in polyphenol content (756.21±6.72 mg GAE/1 g of extract). CONCLUSION: The current study demonstrates for the first time that aqueous Tetraclinis articulata extract has a potent the glucose-lowering effect.

Antihypertensive and vasorelaxant effects of Rumex vesicarius (L.) through receptor-operated calcium channels in hypertensive rats.

AIMS: The aim of the study was to assess the antihypertensive activity of Rumex vesicarius. BACKGROUND: The genus Rumex (sorrel, Polygonaceae), containing approximately 200 species, is distributed worldwide (African, European, Asian, and American countries). It is widely used in traditional medicine as analgesic, diuretic, antispasmodic, and antihypertensive plants. OBJECTIVE: This study aimed to assess the possible antihypertensive vasorelaxant capacity and effect on angiotensin-converting enzyme 2 (ACE-2) of the aqueous extract of Rumex vesicarius (R. vesicarius). MATERIAL AND METHODS: In the present study, the aqueous extract of R. vesicarius (AERV) was prepared, its antihypertensive activity was examined in N(ω)-nitro-L-arginine methyl ester(L-NAME)-induced hypertensive rats, and its vasorelaxant ability along with its effect on stimulating or inhibiting ACE-2 were performed in isolated rat thoracic aorta. RESULTS: The results indicated that AERV decreased the systolic, diastolic, mean, and mean arterial blood pressure in hypertensive rats. The data revealed that AERV exerted its antihypertensive effect through vasodilatory properties via an endothelium-independent pathway. Interestingly, the study demonstrated that the vasorelaxation ability of AERV might be mediated through receptor-operated calcium channels (ROCC). However, AERV extract had no effect on either stimulating or inhibiting ACE-2. CONCLUSION: The present study demonstrates clearly the antihypertensive and vasorelaxant activities of R. vesicarius in hypertensive rats, supporting its beneficial action as an antihypertensive agent.

Effect of Calamintha officinalis on Vascular Contractility and Angiotensinconverting Enzyme-2.

AIMS: The study aimed to assess the antihypertensive activity of Calamintha officinalis. BACKGROUND: Calamintha officinalis (CO) is a medicinal and aromatic herb as well as an antihypertensive plant that is widely used for its medicinal properties in several regions. OBJECTIVE: This study aimed to evaluate the effect of the aqueous extract of Calamintha officinalis (AECO) on vasorelaxant activity and arterial blood pressure under normal and hypertensive states in rats. Additionally, the effect of AECO on vascular angiotensin-converting enzyme 2 (ACE-2) was assessed. METHODS: In the current study, AECO (100 mg/Kg) was prepared, and its antihypertensive ability was assessed in L-NG-Nitro arginine methyl ester (L-NAME)-induced hypertensive rats. Blood pressure and heart rate were recorded for 6 h for the acute experiment and during seven days for the subchronic treatment. RESULTS: The results indicated that AECO reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. In addition, the study showed that AECO exerts a vasorelaxant ability through the sGC-cGMP induction pathway, vascular cyclooxygenase pathway, and the opening of K+ channels. However, AECO had no inhibitory effect on aortic ACE-2. CONCLUSION: The study illustrates the beneficial action of AECO as an antihypertensive and vasorelaxant agent.

Oakmoss Exhibits Antihyperglycemic Activity in Streptozotocin-Induced Diabetic Rats.

AIMS: The study aimed to assess the antidiabetic effect of Oakmoss. BACKGROUND: Lichens species are dual organisms consisting of a mycobiont (Fungi) and a photoautotrophic partner (Algae). They are widely used in traditional medicine as a treatment against diabetes. OBJECTIVE: This study was designed to assess the antihyperglycemic activity as well as the antihyperlipidemic capacity of Oakmoss (Evernia prunastri (L.)) in normal and streptozotocin(STZ)-induced diabetic rats. METHODS: This study has evaluated the effects of aqueous extract of Oakmoss at a dose of 60 mg/kg on blood glucose levels and lipid profile in normal and STZ-induced diabetic rats. Histopathological examination of liver, determination of glycogen content in liver and skeletal muscles (EDL and soleus), antioxidant activity, and phytochemical investigation were also performed. RESULTS: Both single and repeated oral doses of Oakmoss (60 mg/kg) produced a significant reduction of blood glucose, triglycerides and very low-density lipoprotein (VLDL) levels in diabetic rats. Furthermore, repeated oral administration of Oakmoss during 7 days ameliorated the liver function by increasing its glycogen content and improving its histological architecture in treated diabetic rats. In addition, the aqueous extract of Oakmoss exhibited an antioxidant activity and showed richness in certain phytochemicals especially in phenolic acids and flavonoids. CONCLUSION: Oakmoss, a lichen species, exhibits a potential effect on improving hyperglycemia and hypertriglyceridemia in diabetic rats.

Aqueous Extract of Brassica rapa Exerts Antihyperglycemic Activity in Streptozotocin-induced Diabetic Rats.

AIMS: The aim of the study was to assess the antihyperglycemic effect of Brassica rapa. BACKGROUND: Brassica rapa (turnip) is used as an antidiabetic plant. OBJECTIVE: This work aimed to evaluate the effect of the aqueous extract of Brassica rapa seeds (AEBRS) on glycemia in vivo. METHODS: The effect of AEBRS (60 mg/kg) on glycemia and lipid profiles was evaluated. Besides, preliminary phytochemical analysis and the in vitro antioxidant effect were evaluated. RESULTS: AEBRS caused a significant reduction in blood glucose levels in diabetic rats (p<0.0001). In contrast, no significant effect was observed on lipid profiles, whereas antioxidant potential of this extract has been shown. Phytochemical analysis showed the presence of many important phytochemical families. CONCLUSION: The present study shows that AEBRS has a potent antihyperglycemic ability in diabetic rats.

Vitamin C Inhibits Angiotensin-Converting Enzyme-2 in Isolated Rat Aortic Ring.

AIMS: The study aimed to assess the inhibitory effect of Vitamin C on angiotensin-converting enzyme 2. BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses angiotensin-converting enzyme 2 (ACE-II) as the first route to infect human cells. Accordingly, agents with potential inhibition of ACE-II receptors might be effective in the prevention and management of COVID-19. OBJECTIVE: The goal of this work was to assess the possible inhibitory effect of ACE-II on ascorbic acid using an ex vivo approach based on the inhibition of diminazene-induced vasorelaxation. MATERIALS AND METHODS: In the present study, diminazene was used as a known specific inhibitor of ACE-II. Then, the vasorelaxant effect of ascorbic acid on diminazene-induced relaxation was examined using isolated aortic rings. All experiments of this study were evaluated on isolated aortic rings precontracted by epinephrine. RESULTS: The results confirmed that diminazene-induced vasorelaxation in a dose-dependent manner. More interestingly, ascorbic acid inhibited diminazene-induced vasorelaxation in a dose-dependent manner. CONCLUSION: This investigation provides valuable experimental proof of the efficacy of ascorbic acid (Vitamin C) on inhibiting ex vivo vascular angiotensin-converting enzyme II, which is known among the pharmacological targets of anti-COVID-19 drugs.

Antihyperglycemic Activity of Aqueous Extract of Euphorbia guyoniana in Streptozotocin-Induced Diabetic Rats.

AIMS: This work assessed the antihyperglycemic effect of Euphorbia guyoniana. BACKGROUND: Euphorbia guyoniana (Boss. and Reut.) is widely used in traditional medicine. OBJECTIVE: This study was designed to confirm this traditional use by assessing its antihyperglycemic capacity in vivo. METHODS: The effect of the aqueous extract of Euphorbia guyoniana (Boss. and Reut.) (60 mg/kg) on glycemia in both normal and diabetic rats was evaluated. The glycogen content in the liver and skeletal muscles (extensor digitorum longus and soleus) was measured. Furthermore, liver histopathological analysis was performed. RESULTS: The findings showed that Euphorbia guyoniana (Boss. and Reut.) exhibited a significant decrease in glycaemia in diabetic rats (from 20±2 mmol/l to 5.5 mmol/l after 6 hours of oral administration; p<0.0001 and from 20±2 mmol/l to 4.5 mmol/l after 7 days of once-daily repeated oral administration of the aqueous Euphorbia guyoniana extract; p<0.0001). In addition, the extract increased the glycogen content in the liver (41±4 mg/g versus 70±5 mg/g in normal and diabetic rats respectively) and extensor digitorum longus (39±4 mg/g versus 60±1 mg/g in normal and diabetic rats, respectively), and partially restored corporal weight in diabetic rats. Furthermore, this aqueous extract has been shown to suppress hyperglycemia induced by glucose load in treated diabetic rats. Additionally, hepatic histology in diabetic rats has been improved. This plant revealed the presence of several phytochemical constituents and possessed antioxidant activity. CONCLUSION: The current study evidenced that Euphorbia guyoniana (Boss. and Reut.) has a beneficial effect on improving hyperglycemia and glycogen depletion in the diabetic state.

Phytocompounds from Anvillea radiata as promising anti-Covid-19 drugs: in silico studies and in vivo safety assessment.

As an alternative strategy in combating the COVID-19 pandemic, phytoconstituents from medicinal plants are getting attention worldwide. The current investigation focused on the efficacy of the essential phytocompounds identified in Anvillea radiata to target the main protease (Mpro) of SARS-COV-2 through molecular docking and dynamic analyses; in addition to the safety assessment of this herb in vivo. In silico, the 6LU7 structure of Mpro was prepared as a target by Discovery Studio 2020. The virtual screening of phytocompounds from Anvillea radiata was performed through iGEMDOCK program, followed by an evaluation of the potential inhibitors based on the docking scores calculated using AutoDock Vina and MGL Tools programs, as well as complexes stability assessment through MD simulation. In vivo toxicity studies of Anvillea radiata aqueous extract were also conducted in Wistar rats. Among the phytocompounds evaluated in this study, 3,5-Dicaffeoylquinic acid, Spinacetin, 9α-Epoxyparthenolide, Hispidulin, Quercetin, jaceosidin, Nepetin, and isorhamnetin were predicted to have the highest binding affinity for the Main protease (Mpro) target of SARS-CoV-2. The aqueous extract of Anvillea radiata did not induce any signs of toxicity. 3,5-Dicaffeoylquinic acid, Spinacetin, 9α-Epoxyparthenolide, jaceosidin, and isorhamnetin from Anvillea radiata were selected as potential inhibitors of SARS-Cov-2 to develop new drugs anti-COVID-19.