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.

Moroccan Antihypertensive Plants and their Mechanisms of Action.

BACKGROUND: The use of herbal remedies, medicinal plants, and their derivatives for the treatment and control of hypertension is well-known and widespread throughout Morocco. AIMS: The aim of the study was to review the antihypertensive and vasorelaxant medicinal plants of the Moroccan pharmacopeia. OBJECTIVE: To date, no review on Moroccan medicinal plants exhibiting antihypertensive effects has been performed, and their mechanism of action has not been specified. The objective of this review was to collect, analyze, and critically assess published publications on experimental and clinical research that explored the blood pressure-reducing abilities of Moroccan medicinal plant extracts. MATERIALS AND METHODS: This study collected, processed, and critically analyzed published studies related to experimental and clinical research that investigated Moroccan herbal derivatives' blood pressure-lowering abilities using a number of scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, and others. Plantlist.org was used to validate the right plant names. RESULTS: The results revealed 22 species of Moroccan medicinal plants belonging to 13 different groups with recognized antihypertensive properties. The species were abundant in a variety of chemical elements. Asteraceae (08 species), Lamiaceae (3 species), Apiaceae (2 species), and 1 species each from the following families: Parmeliaceae, Fabaceae, Cistaceae, Malvaceae, Polygonaceae, Brassicaceae, Myrtaceae, Rutaceae, Amaranthaceae, Rosaceae, and Lauraceae were the most frequently mentioned families for their antihypertensive properties. The most used parts were the leaves and the aerial parts. The two main methods of preparation among Moroccans were decoction and infusion. This study demonstrated the known antihypertensive and vasorelaxant properties of Moroccan medicinal plants in vivo and in vitro, as well as their mechanisms of action. Interestingly, phytochemicals can operate on blood vessels directly via a vasorelaxant impact involving a range of signaling cascades or indirectly by blocking or activating multiple systems, such as an angiotensin-converting enzyme (ACE), renin-angiotensin system (RAS), or diuretic activity. CONCLUSION: The review of the available data reveals that more work needs to be done to examine all the Moroccan medicinal plants that have been suggested as antihypertensive in published ethnopharmacological surveys. A review of the literature in this area reveals that methodologies of the experimental study need to be standardized, and purified molecules need to be studied. In addition, mechanistic investigations, when they exist, are generally incomplete. In contrast, only a few advanced clinical investigations have been conducted. However, all studies fail to determine the efficacy/safety ratio.

Comprehensive Review on the Genus Haloxylon: Pharmacological and Phytochemical Properties.

AIMS: This review aimed to review the biological, pharmacological, and phytochemical aspects of the genus Haloxylon. BACKGROUND: Plants of the genus Haloxylon have been used for a long time in traditional medicine, and they are distributed in the western Mediterranean region to the Middle East, Iran, Mongolia, Burma, and southwest China. The studied parts of Haloxylon species include aerial parts, leaves, branches, seeds, roots, rhizosphere, soil, and whole plants, used to treat several diseases, including sexual disorders, hepatobiliary disorders, eye disorders, skin diseases and hemorrhoids, diarrhea, and effective in the treatment of various ailments such as snake bite, stomach ache, diabetes, wounds, earache and sciatica pain, windbreak dune fixation, feeding of livestock and firewood. OBJECTIVES: Till now, no review on the genus Haloxylon has been conducted. This review aimed to provide updated information on the genus Haloxylon, including traditional medicinal uses, valorization and exploitation of medicinal plants, phytochemistry, botanical characterization, pharmacological and toxicological research focusing on the medicinal properties of several Haloxylon species, especially their antioxidant, antibacterial, anti-inflammatory, cytotoxic and antifungal activities, as well as the effect of each bioactive molecule isolated from these species and their pharmacological use, including the preclinical evaluation of new drugs. MATERIALS AND METHODS: The present work was conducted using various scientific databases, including Science Direct, Scopus, PubMed, Google Scholar, etc. Correct plant names were verified from plantlist.org. The results of this search were interpreted, analyzed, and documented based on the obtained bibliographic information. RESULTS: Among all species of the Chenopodiaceae family, 6 species of the Haloxylon genus have approved antioxidant activity, 5 species have antibacterial activity, 3 species have anti-inflammatory activity, 2 species have cytotoxic activity, and 3 species have antifungal activity. The majority of the chemical constituents of this plant include flavonoids, alkaloids, phenols, saponins, glycosides, and tannins. Among them, the main bioactive constituents would be present in the alkaloid fraction. The study of more than 9 Haloxylon plants has identified more than 46 compounds. Pharmacological research proved that crude extracts and some pure compounds obtained from Haloxylon had activities for the treatment of different diseases. The objective of the present study was focused on antioxidant, antibacterial, anti-inflammatory, cytotoxic and antifungal diseases. From the study of the phytochemistry of the Haloxylon family, it was concluded that all studied plants had active compounds. Among them, 11 isolated molecules have medicinal activities with antioxidant properties, 10 molecules showed antibacterial effects, more than 6 molecules have anti-inflammatory properties, more than 9 isolated molecules have medicinal activities against cytotoxic diseases, and more than 28 molecules have antifungal effects. Therefore, the safety of Haloxylon herbal medicine should be considered a top priority in the early stages of development and clinical trials. CONCLUSION: Several previously conducted studies have validated multiple traditional uses of Haloxylon species. Further research is needed on Haloxylon plants before they can be fully utilized in the clinic as a potent drug candidate, as researchers are mainly focusing on alkaloids, diterpenoids, and triterpenoids, whereas there are many other types of compounds that may possess novel biological activities.

The Genus Anabasis: A Review on Pharmacological and Phytochemical Properties.

The genus Anabasis has long been used in phytomedicine. The studied parts of Anabasis species are used as antirheumatic, diuretic, antidotes against poison, anti-erosion, anti-ulcer, and antidiabetic agents, as well as against headache and skin diseases. The objective of the present review was to summarize the phytochemical and pharmacological aspects related to the genus Anabasis. The results of this literature analysis show that among all the species of the Anabasis (A) family, A. aphylla, A. Iranica, A. aretioides, and A. articulata showed antibacterial activity; A. aretioides and A. articulata have antioxidant activity, A. aretioides and A. articulata have antidiabetic activity, A. articulata has cytotoxic activity and A. setifera, A. aretioides, and A. articulata exhibit anti-inflammatory activity. The Anabasis genus contains saponins, and alkaloids, such as anabasine, anabasamine, lupinine, jaxartinine, and triterpenic sapogenins. The study of 15 Anabasis plants has identified 70 compounds with an array of pharmacological activities especially antibacterial, antioxidant, antidiabetic, cytotoxic, and anti-inflammatory activities. However, there is a need for further studies on Anabasis plants before they can be fully used clinically as a potential drug.

A Comprehensive Overview of Hibiscus rosa-sinensis L.: Its Ethnobotanical Uses, Phytochemistry, Therapeutic Uses, Pharmacological Activities, and Toxicology.

Hibiscus rosa-sinensis (H. rosa-sinensis) has been largely used in traditional medicine. This study aims to review the pharmacological and phytochemical properties of Hibiscus rosa-sinensis L and also summarize the pharmacological, photochemical, and toxicological characteristics of H. rosa-sinensis. The current review focuses on the distribution, chemical content, and main uses of H. rosa-sinensis. Various scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, etc., were used. Correct plant names were verified from plantlist.org. The results were interpreted, analyzed, and documented based on bibliographic information. This plant has been frequently used in conventional medicine due to its high concentration of phytochemicals. All its parts contain numerous chemical compounds, such as flavonoids, tannins, terpenoids, anthocyanins, saponins, cyclopeptide alkaloids, and vitamins. More interestingly, the roots of this plant contain glycosides, tannins, phytosterols, fixed oils, fats, flavonoids, saponins, gums, and mucilages. The leaves contain alkaloids, glycosides, reducing sugars, fat, resin, and sterols. The stem contains other chemical compounds, such as ß-sitosterol, teraxeryl acetate, cyclic sterculic, and malvalic acids. Finally, the flowers contain riboflavin, thiamine, apigenidine, oxalic acid, citric acid, quercetin, niacin, pelargonidine, and ascorbic acid. This species has a wide variety of pharmacological applications, such as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, antihypertensive, antifertility, antifungal, anticancer, hair growth-promoting, antihyperlipidemic, reproductive, neurobehavioral, antidepressant, and antipyretic activities. Finally, toxicological studies have shown that higher doses of extracts from the plant are safe.

Alkaloids as Promising Agents for the Management of Insulin Resistance: A Review.

BACKGROUND: Insulin resistance is one of the main factors that lead to the development of type 2 diabetes mellitus (T2DM). The effect of alkaloids on insulin resistance has been extensively examined according to multiple scientific researches. OBJECTIVE: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes. METHODS: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids. RESULTS: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and ß-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of ß-cell function (HOMA-ß) are recognized as robust markers of insulin sensitivity and ß-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers. CONCLUSION: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Study of the Antihypertensive Effect of Scorzonera undulata ssp. deliciosa in Albino Wistar Rats.

AIMS: The study aimed to investigate the antihypertensive activity of Scorzonera undulata ssp. deliciosa. BACKGROUND: Scorzonera undulata ssp deliciosa, locally known as "Guiz", is used in traditional medicine in Morocco as a diuretic and mainly against snake bites. OBJECTIVE: This study investigated the possible antihypertensive effect of the aqueous extract of Scorzonera undulata (AESU). MATERIAL AND METHODS: In the present study, the antihypertensive activity of AESU AUSU was tested in normotensive and hypertensive rats. RESULTS: The results indicated that AESU decreased the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. The data revealed that AESU exerted its antihypertensive effect through vasodilatory properties. Interestingly, the study demonstrated that the vasorelaxation ability of AESU might be mediated through receptor-operated calcium channels (ROCCs). However, AESU dhad effect on inhibiting ACE-2. CONCLUSION: The present study indicates the antihypertensive and vasorelaxant activities of AESU in hypertensive rats.

Potential Antihypertensive Activity of the Aqueous Extract of Ammi visnaga and its Effect on ACE-2 in Rats.

AIMS: This work aimed to investigate the antihypertensive activity of Ammi visnaga. BACKGROUND: The aqueous extract of Ammi visnaga has traditionally been used to treat hypertension in Morocco. OBJECTIVE: The objective of this investigation was to evaluate the effect of Ammi visnaga aqueous extract (AVAE) on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of Ammi visnaga on vasodilatation was assessed in isolated rat aortic rings with functional endothelium pre-contracted with epinephrine EP or KCl. METHODS: AVAE was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received oral AVAE at two selected doses of 70 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. RESULTS: AVAE lowered blood pressure only in L-Name-induced hypertensive rats. Furthermore, AVAE (0.375-1.375 mg/ml) showed a vasodilator effect in isolated aortic rats. In addition, not all of the medications used in our study were responsible for the signaling pathway. As a result, additional pharmaceuticals are required to confirm the mechanism of this signaling pathway. CONCLUSION: The aqueous extract of Ammi visnaga exerts an interesting antihypertensive activity, which could be mediated through its vasorelaxant activity. The study supports its use as a medicinal plant against hypertension in Morocco.

Ethnopharmacology, Nutritional Value, Therapeutic Effects, Phytochemistry, and Toxicology of Salvia hispanica L.: A Review.

AIMS: The purpose of this review was to emphasize the nutritional value, and pharmacological and phytochemical properties of Salvia hispanica, as well as its toxicological evaluation. BACKGROUND: Salvia hispanica L. (S. hispanica), also called chia seeds, is an annual herbaceous plant belonging to the family Lamiaceae. It is a species of medicinal and dietary plant used since ancient times by the Maya and Aztecs. Its product is an indehiscent dry fruit that is commonly called a seed. It is utilized for its health benefits and uses in cooking. OBJECTIVE: The study aimed to investigate the pharmacological, phytochemical, and toxicological properties of S. hispanica seeds. The research also attempted to explore and compile all existing knowledge and data on these seeds' nutritional value and medical applications. MATERIALS AND METHODS: The current review was conducted using numerous scientific databases, including Science Direct, Scopus, PubMed, Google Scholar, etc. The correct plant name was verified from plantlist.org. The results of this search were interpreted, analyzed, and documented based on the obtained bibliographic information. RESULTS: S. hispanica is a pseudo cereal that is consumed by the world's population because of its preventive, functional, and antioxidant characteristics, attributable to the presence of lipids, dietary fiber, protein, phenolic compounds, vitamins, and minerals. According to research, chia offers hypoglycemic, antimicrobial, anticancer, anti-inflammatory, antioxidant, antihypersensitive, anti-obesity, and cardioprotective properties. Chia consumption has grown because of its favorable benefits on obesity, cardiovascular disease, diabetes, and several forms of cancer. These advantages are mostly due to the high concentration of essential fatty acids, dietary fiber, antioxidants, flavonoids, anthocyanins, vitamins, carotenoids, and minerals found in this seed. Based on the beneficial components, chia seeds have enormous potential in the areas of health, food, animal feed, medicines, and nutraceuticals. Finally, toxicological investigations have indicated the greater doses of chia seed extracts as safe. CONCLUSION: The current evaluation has focused on the distribution, chemical composition, nutritional value, and principal uses of S. hispanica in order to determine future research requirements and examine its pharmacological applications through clinical studies.

Mentha pulegium: A Plant With Several Medicinal Properties.

The species Mentha pulegium L. (M. pulegium L.) belongs to the family Lamiaceae, native to Europe, North Africa, and the Middle East, and the genus Mentha. It has been traditionally used in food, cosmetics, and medicines. It is a perennial, fragrant, well-liked, herbaceous plant that can grow up to half a meter tall. It is extensively used as a food flavoring, particularly for Moroccan traditional drinks. Chewing mint and M. pulegium, a relaxing and refreshing plant, can be used to treat hiccups and act as an anticonvulsant and nerve relaxant. Pennyroyal leaves that have been crushed have a pungent, spearmint-like scent. Pennyroyal is used to make herbal teas, which, while not proven to be harmful to healthy adults in small doses, are not recommended due to their liver toxicity. Infants and children can die if they consume it. Pennyroyal leaves, both fresh and dried, are particularly effective at repelling insects. Pennyroyal essential oil should never be taken internally because it is highly toxic, even in small doses, it can be fatal. This plant is used in traditional Moroccan medicine to treat a wide range of conditions, including influenza, rheumatism, migraine, infertility, ulcer, pain, gastrointestinal problems, fever, diabetes, obesity, mental and cardiac disorders, constipation, respiratory ailments, and cough. M. pulegium is a great candidate for contemporary therapeutic usage since it contains a wide variety of biologically active compounds, including terpenoids, flavonoids, alkaloids, tannins, and saponins in all its parts. Among the different parts used are the whole plant, the aerial part, the stem, and the leaves. More interestingly, the entire plant contains a variety of compounds including Pulegone, Isomenthone, Carvone, Menthofuran, Menthol, 1,8-Cineole, Piperitone, Piperitenone, Neomenthol, -humulene, and 3-octanol. Eriocitrin, Hesperidin, Narirutin, Luteolin, Isorhoifolin, Galic acid, and Rosmarinic acid are found in the leaves. p-hydroxybenzoic acid, Ferulic acid, Caffeic acid, Vanillic acid, Syringic acid, Protocatechuic acid, Cinnamic acid, Phloretic acid, o-coumaric acid, p-coumaric acid, Catechin, Epicatechin, Chrysin, Quercetin, Naringenin, Carvacrol are all found in the areal part. Alterporriol G, Atropisomer, Alterporriol H, Altersolanol K, Altersolanol L, Stemphypyrone, 6-O-methylalaternin, Macrosporin, Altersolanol A, Alterporriol E, Alterporriol D, Alterporriol A, Alterporriol B, and Altersolanol J are also found in the stem of fungus. Pulegone, Piperitone, p-menthane-1,2,3-triol, ß-elemenene, guanine (cis-), Carvacrol acetate, and Phenyl ethyl alcohol are all components of this plant's essential oils. Moreover, the study also sought to investigate and document all currently available evidence and information on the nutritional composition and therapeutic uses of this plant ornamental. Its pharmacological applications include antimicrobial, antioxidant, antihypertensive, antidiabetic, anti-inflammatory, antiproliferative, antifungal, anticancer, burn wound healing, antispasmodic, and hepatotoxicity. Finally, toxicological studies have revealed that while low doses of extracts of the plant M. pulegium are not toxic, however, its essential oils of it are extremely toxic. In order to evaluate future research needs and investigate its pharmacological applications through clinical trials, the current assessment focuses on the distribution, chemical composition, biological activities, and primary uses of the plant.

Antidiabetic Effect of Star Anise (Illicium verum) in Streptozotocin-induced Diabetic Rats.

AIM: The current study aimed to evaluate the antidiabetic potential of Illicium verum fruits. BACKGROUND: Illicium verum fruits are frequently used by the Moroccan population in the treatment of diabetes. METHODS: The antihyperglycemic effect of the aqueous extract of Illicium verum fruits (AEIVF) in rats was assessed. The effects of AEIVF (20 mg/kg) on glycemia and lipid profile as well as its phytochemical and antioxidant properties were evaluated. RESULTS: In normal and diabetic rats, AEIVF reduced blood glucose levels 6 hours after administration. Furthermore, after 7 days of treatment, glycemia was lowered in diabetic rats, and this extract exhibited an antioxidant activity. CONCLUSION: The study shows that Illicium verum possesses a potent antidiabetic activity. In addition, the toxicity of AEIVF was evaluated and the LD50 value was found to be greater than the 2 g/kg dose.

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.

Study of the Analgesic Potential of the Ethanolic Extract of Moroccan Cistus ladanifer L.

AIMS: The study aimed to analyze the analgesic activity of Cistus ladanifer L. BACKGROUND: Cistus ladanifer L. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects. OBJECTIVES: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladanifer L. (C. ladanifer) collected in Northern Morocco. METHODS: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test. RESULTS: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p <0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin). CONCLUSION: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

Antihyperglycemic Effect of Rhamnus alaternus L. Aqueous Extract in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Traditionally, the aerial parts of Rhamnus alaternus L. have been widely used in Mediterranean countries, including Morocco, to cure diabetes. AIM: This study aimed to evaluate the antidiabetic effect of Rhamnus alaternus aqueous extract in streptozotocin(STZ)-induced diabetic rats. OBJECTIVE: This work aimed to evaluate the antihyperglycemic effect of Rhamnus alaternus aqueous extract (RAAE) in normal and diabetic rats. Then the phytochemical composition, antioxidant capacity, and potential toxicity of RAAE were also assessed. METHODS: The effects of acute (6 h) and subchronic (7 days) oral administration of RAAE (20 mg/kg) on blood glucose levels and lipid profiles were evaluated in normal and diabetic rats. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity, using the DPPH method, were evaluated. Additionally, the toxicity of the aqueous extract (5 mg/kg) was also studied and the LD50 value was determined. RESULTS: RAAE (20 mg/kg) over 7 days of oral administration significantly decreased the blood glucose levels both in normal and diabetic rats. In diabetic rats, this extract also improved oral glucose tolerance. In addition, RAAE possessed significant antioxidant activity. According to preliminary phytochemical research, RAAE contains several chemical compounds, including alkaloids, polyphenols, flavonoids, cyanidins, anthraquinones, and sterols. On the other hand, the quantitative phytochemical study of the aqueous extract revealed a considerable amount of total phenolic compounds (497.93 ± 3.38 mg GAE/1g of RAAE), flavonoids (100.42 ± 0.32 mg RE/ g of RAAE), and tannins (14.32 ± 0.37 mg CE/1g of RAAE). CONCLUSION: We conclude that RAAE exerts a significant antihyperglycemic effect in STZ-induced diabetic rats at a low dose. Indeed, more research is still required to support the use of this plant in the Moroccan population's diabetes care.

Antihypertensive Effect of Euphorbia cheiradenia in Rats.

AIMS: The study aimed to investigate the effect of Euphorbia cheiradenia on blood pressure. BACKGROUND: Euphorbia cheiradenia is a medicinal plant with several medicinal properties. OBJECTIVE: This study aimed to study the vasorelaxant and antihypertensive capacity of the aqueous extract of Euphorbia cheiradenia (E. cheiradenia), and to evaluate its effect on angiotensinconverting enzyme 2 (ACE2). METHODS: The antihypertensive ability of aerial parts of the aqueous extract of E. cheiradenia (AEEC) was investigated in L-NAME-induced hypertensive rats, and its vasorelaxant effect was performed on the isolated thoracic rat aorta. In addition, the possible inhibitory effect of AEEC on ACE2 was also studied. RESULTS: AEEC lowered blood pressure parameters in hypertensive rats. The study of the vasorelaxant activity revealed that AEEC partially relaxed the aortic rings through activation of the KATP channel and inhibition of the ß-adrenergic pathway. Whereas pretreatment of aortic rings with nifedipine, indomethacin, L-NAME, and methylene blue did not attenuate AEEC-induced vasorelaxation. However, AEEC did not affect ACE2 in isolated rat aortas. CONCLUSION: The study showed that aqueous E. cheiradenia extract exhibits significant antihypertensive activity in hypertensive rats.

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.

Ammodaucus leucotrichus Acts as an Antihypertensive and Vasorelaxant Agent Through sGC and Prostaglandin Synthesis Pathways.

BACKGROUND: Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension. AIMS: The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus. OBJECTIVE: The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats. METHODS: ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action. RESULTS: The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 µM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation. CONCLUSION: Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

Salvia aucheri Exhibits Antihypertensive Activity in Hypertensive Rats.

AIMS: The present work aimed to assess the antihypertensive activity of Salvia aucheri. BACKGROUND: Salvia aucheri (S. aucheri) is an aromatic and medicinal herb belonging to the Lamiaceae family. In Morocco, this plant is locally used for used to treat stomach, digestive disorders, rheumatism, and hypertension. Nevertheless, the effect of Salvia aucheri on hypertension has not yet been studied. OBJECTIVE: The objective of this investigation was to evaluate the beneficial effect of the aqueous extract of S. aucheri leaves on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of S. aucheri leaves on vasodilatation was assessed in isolated rat aortic rings with functional endothelium precontracted with epinephrine EP or KCl. METHODS: The aqueous extract of the aerial parts of S. aucheri (AESA) was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received AESA orally at two selected doses of 100 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. RESULTS: The results indicated that AESA significantly reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats over both single and repeated oral administration. However, AESA did not change the blood pressure parameters in normotensive rats. Concerning the results of vasorelaxant activity, the results showed that AESA was able to provoke potent vasorelaxant ability, which seems to be mediated through direct nitric oxide (NO) and NO-cyclic guanosine monophosphate pathways. CONCLUSION: The study elucidates the beneficial action of AESA as an antihypertensive and vasorelaxant agent.

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.

Antihyperglycemic and Antidyslipidemic Effects of Artemisia arborescens Aqueous Extract on Streptozotocin-induced Diabetic Rats.

AIMS: This study aimed to investigate the antidiabetic activity of Artemisia arborescens. BACKGROUND: Artemisia arborescens is an aromatic, medicinal, and endemic plant mostly found in the Mediterranean region. This plant is widely used as alternative medicine. OBJECTIVE: The study was designed to examine the antihyperglycemic and antihyperlipidemic activities of Artemisia arborescens aqueous extract (AEAA) in normal and streptozotocin (STZ)- induced diabetic rats. METHODS: The effect of AEAA (40 mg/kg and 80 mg/kg) on plasma glucose levels and plasma lipid profile was investigated in normal and STZ-induced diabetic rats. The plasma glucose levels were determined after a single (6 hours) and subchronic oral administration (7 days), and plasma lipid profiles were evaluated after both acute and subchronic oral administration. Additionally, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus muscles was measured using a standard method. Moreover, the aqueous extract was tested for its 1.1-diphenyl-2- picrylhydrazyl (DPPH) radical-scavenging activity. RESULTS: In diabetic rats, AEAA oral administration (40 mg/kg and 80 mg/kg) produced a significant decrease in blood glucose levels after 7 days of oral administration (P<0.0001). Moreover, a significant decrease in plasma triglyceride levels was reported on the last day of treatment by AEAA (80 mg/kg) (P<0.05). Furthermore, a significant decrease in total cholesterol levels was observed after 7 days of AEAA oral administration in diabetic rats (P<0.01). Moreover, a significant increase in HDL-c concentration was noted after one week of AEAA (80 mg/kg) oral administration (P<0.001). In addition, AEAA oral administration (80 mg/kg) significantly increased the glycogen content in the liver and extensor digitorum longus (P<0.05). On the other hand, qualitative and quantitative phytochemical screenings revealed the presence of various compounds, such as polyphenols, flavonoids, and tannins. CONCLUSION: In summary, the study demonstrates that Artemisia arborescens oral administration exhibited a significant antihyperglycemic effect on diabetic rats and revealed a significant amelioration in lipid profile and glycogen content.