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.

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.

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.

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.

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.

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.

Traditional Uses, Pharmacological, and Phytochemical Studies of Euphorbia: A Review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Euphorbia have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan for their great medicinal value and health benefits. Their stems, leaves, roots, and latex are widely used to treat respiratory infections, body and skin irritations, digestive disorders, inflammatory infections, body pain, snake or scorpion bites, pregnancy, sensory disturbances, microbial and anticancer diseases. OBJECTIVES: This review aims to provide updated information on the genus Euphorbia, including traditional medicinal uses, valuation and exploitation of medicinal plants, phytochemistry, botanical characterization, pharmacological and toxicological research focused on the medicinal properties of several Euphorbias in particular their antibacterial, anti-tumor, and cell manifestations, in addition to the effect of each isolated bioactive molecule from these species and their pharmacological use including preclinical evaluation of new drugs. MATERIALS AND METHODS: This work was conducted using scientific databases such as: PubMed, Google Scholar, Scopus, Science Direct, etc. In addition, ChemDraw software has been used for the drawing of chemical molecules. The correct names of the plants were confirmed from plantlist.org. The results of this review research were interpreted, analyzed and documented based on the bibliographical information obtained. RESULTS: Among all the species of the Euphorbiaceae family, 15 species have been demonstrated to exhibit anticancer activity, 21 species have antibacterial activity, and 10 species have cytotoxic activity. The majority of the chemical constituents of this plant include triterpenoid glycosides, diterpenoids, flavonoids, and the 4α-methyl steroids. Among them, the main bioactive constituents are present in the diterpenoid fraction. The study of more than 33 steroid plants identified more than 104 compounds. Pharmacological research proved that the crude extracts and some pure compounds obtained from Euphorbia had activities for the treatment of different diseases. The objective of the present study was focused on cytotoxic, antibacterial and antitumor diseases. The study of the phytochemistry of the Euphorbia families led to the conclusion that all the plants studied had active compounds, of which 27 plants were characterized by their cytotoxic effects, 7 had antibacterial effects and 10 plants had anti-tumor activities. Therefore, the safety of Euphorbia herbal medicine should be considered a top priority in the early stages of development and clinical trials. CONCLUSION: Many previous studies have validated many traditional uses of Euphorbia species. The latex of some Euphorbia species seems to be toxic however, studies dealing with the safety and quality of these species are still incomplete. Extensive studies are needed on the Euphorbia plants before they can be fully used in clinics as a potent drug candidate, as researchers are focusing mainly on diterpenoids and triterpenoids, while there are many other types of compounds that may possess new biological activities.

Antihypertensive and Vasorelaxant Effects of Hibiscus rosa-sinensis through Angiotensin-Converting Enzyme-2 (ACE-2), and Ca2+ channels Pathways.

AIMS: The aim of the study was to assess the antihypertensive activity of Hibiscus rosa-sinensis. BACKGROUND: Hibiscus rosa-sinensis is used traditionally to treat hypertension. OBJECTIVE: The goal of the study was to investigate the effect of the aqueous extract of Hibiscus rosa-sinensis flowers (AEHRS) on resting blood pressure in rats. MATERIAL AND METHODS: In the present study, AEHRS was prepared and its antihypertensive activity was evaluated using in vivo and in vitro studies. In the in vivo study, hypertensive and normotensive rats were treated by AEHRS (100 mg/kg) orally for 6 hours in the acute treatment and for 7 days in the subchronic treatment. Systolic, diastolic, and mean arterial blood pressure values and heart rate were then recorded using a tail cuff and a computer-assisted monitoring device. To assess the vasorelaxant activity of AEHRS, isolated thoracic aortic rings were suspended in a tissue bath and changes in tension were recorded using a data acquisition system. Potential pathways involved in the vasorelaxant activity were evaluated using several standard pharmacological agents. RESULTS: The results indicated that repeated oral administration of AEHRS during 7 days lowered systolic, diastolic, and mean arterial blood pressure in hypertensive rats without affecting normotensive rats. Furthermore, the data revealed that AEHRS exerts vasorelaxant properties via an endothelium-independent pathway. More interestingly, the study demonstrates that the vasorelaxant capacity of AEHRS seems to be exerted through the stimulation of angiotensin-converting enzyme-2 (ACE-2) and the inhibition of Ca2+ channels pathway. CONCLUSION: The present study revealed that aqueous extract of Hibiscus rosa-sinensis has a significant antihypertensive activity and that its vasorelaxant effect may be mediated through stimulation of ACE-2, and inhibition of the Ca2+ channels.