Abstract: According to the different efficacy of Chinese herbal medicines, herbal medicines with renin inhibitory effect, angiotensin-converting enzyme inhibitory effect, angiotensin II receptor antagonistic effect and aldosterone receptor antagonistic effect are reviewed to provide a basis for clinical identification and rational use, so as to effectively improve clinical efficacy.
Keywords: Chinese medicine, renin inhibitor, angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor antagonist (ARB), aldosterone antagonism
The renin-angiotensin-aldosterone system (RAAS) is an important neuroendocrine system in the body, which acts extensively on the heart, blood vessels, kidneys, and adrenal glands, and plays a very important role in maintaining normal blood pressure and electrolyte balance. The over-activation of this system is closely related to the occurrence and development of various cardiovascular and renal diseases, and blocking one of these links and targets can effectively stop the progression of these diseases. To date, renin inhibitors, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARB), and aldosterone receptor antagonists (AB) act around different aspects of the RAAS, not only by regulating blood pressure, but also by a range of inflammatory and immune modulation mechanisms. The invention and application of the above mentioned RASS antagonists is one of the most important medical achievements of late.
However, in the long-term application, it was found that there are certain limitations of this class of drugs, such as 1) causing cough, 2) causing high potassium, 3) prohibited in pregnant women because it can cause fetal malformation, 4) prohibited in patients with bilateral renal artery stenosis, 5) avoided in patients with severe renal failure and progressive decrease in glomerular filtration rate, 6) prone to cause hypotension in the first dose, and so on.
After years of exploration, Chinese medicine has its own characteristics and advantages in antagonizing the renin-angiotensin-aldosterone system, and it can be used according to the different types and symptoms of patients, which not only has obvious antagonistic effects, but also can effectively improve various symptoms of patients, which is deeply affirmed by the industry. Now, according to the different efficacy of traditional Chinese medicine, a review of the research of traditional Chinese medicine with antagonistic renin-angiotensin-aldosterone system is made for the clinical and experimental research of the same.
I. RASS antagonists of tonic drugs
Chinese herbal tonic agents include those that benefit qi, warm yang, nourish blood and nourish yin, each of which is used according to the deficiency of qi, blood, yin and yang in human body. Among these drugs, the more studied RASS agents are Astragalus, Epimedium, Angelica, White Peony and American Ginseng.
Astragalus: Sweet in nature, slightly warm. It belongs to the lung and spleen meridians. It is effective in tonifying qi and raising yang, benefiting the guard and fixing the surface, promoting water retention and swelling, and supporting sores and generating muscle. Chemical composition includes astragalus polysaccharide, astragaloside, glucuronide, various amino acids and folic acid, etc. Shi Hailian et al. used narrowed rat abdominal aorta to prepare a model of left ventricular hypertrophy caused by pressure overload, and gave different doses of Astragalus saponin A by instillation for 12 weeks, and found that Astragalus saponin A could upregulate the gene and protein expression of AT2 in myocardial tissue, but had no reversal effect on the upregulated AT1 gene and protein expression in myocardial tissue of model animals, indicating that Astragalus saponin A could inhibit the overactivation of the renin-angiotensin system in rats. It was shown that astragaloside A could inhibit the over-activation of renin-angiotensin system in rats.
Epimedium: Pungent, sweet and warm in nature. It belongs to the kidney and liver meridians. It is effective in tonifying the kidney and strengthening yang, dispelling wind and removing dampness. Total flavonoids of Epimedium (TFE) is a total flavonoid extracted from Epimedium, which mainly contains Epimedium glycosides and Epimedium hypoglycosides. Dong Xiaolei et al. studied the effects of TFE on cardiac function, plasma aldosterone (ALD) and ventricular remodeling in rats with isopropyl adrenaline induced congestive heart failure (CHF) as an experimental model and found that myocardial fibrosis (MF) and cardiac function were significantly decreased in rats with isopropyl adrenaline induced congestive heart failure, while ALD was significantly decreased and MF was significantly improved after TFE intervention. significantly improved. It was suggested that TFE improved the cardiac function and ventricular remodeling in rats with experimental congestive heart failure by reducing plasma ALD.
Angelica sinensis: Sweet, pungent and warm in nature. It belongs to the liver, heart and spleen meridians. Effects: Tonifying blood, regulating menstruation, activating blood circulation, relieving pain, and moistening the bowels. Modern pharmacological experiments have proved that angelica injection has the effects of lowering blood lipids, anti-arrhythmia, dilating blood vessels, improving myocardial ischemia and lowering blood pressure. Using cell biology, Di Mei Xian et al. observed the effect of Angelica injection on angiotensin II-induced cardiomyocyte hypertrophy in mammary rats, and found that Ang II was able to significantly increase the diameter and protein content of cardiomyocytes (P < 0.01), and Angelica injection had a reversal effect on this effect ( P < 0.05). Wang Zhanlian et al [4] found that Angelica needle acupoint injection could reduce plasma renin activity (PRA) and Ang II content in hypertensive rats with chronic nephritis, resulting in a significant decrease in blood pressure. The possible mechanisms of action are:1, acupuncture can reduce PRA , Ang II, and thus the activity of RASS; 2, Angelica can significantly reduce platelet thromboxane B2 (TXB2) in blood, as well as antagonize the effect of RASS, thus reducing its antihypertensive effect.
White peony: bitter, sour and slightly cold in nature. It belongs to the liver and spleen meridians. Effects: Nourishing blood, astringing Yin, softening the liver, relieving pain, and calming liver Yang. Total Glucoside (TGP) is the active ingredient extracted from Paeonia lactiflora, including: paeoniflorin (PF), paeonolactone glucoside, hydroxy paeoniflorin, benzoyl paeoniflorin, paeoniflorin, etc. Feng Ruier et al. experimented with a high-fat and high-sugar diet to replicate the metabolic syndrome-hypertension (MS-Ht) rat model and observed that TGP increased blood pressure and renin, Ang II, TNF-α, endothelin (ET-1) and malondialdehyde (MDA) levels, while NO levels and superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were decreased in MS-Ht rats. Metformin (Met) and TGP can significantly reduce blood pressure and renin, AngII, TNF-α, endothelin (ET)-1 and MDA content in rats, and increase NO content and SOD and NOS activity, suggesting that the antihypertensive mechanism of the drug may also include: inhibition of RAS, antagonism of inflammatory mediators and free radical generation, and enhancement of vasodilator effect.
American ginseng: sweet, slightly bitter and cold in nature. It belongs to the lung, heart, kidney and spleen meridians. Effects: Tonifying Qi, nourishing Yin, clearing heat and generating body fluid. Panax ginseng leaf 20S-protopanaxadiol saponin (PQDS) is a 20S-protopanaxadiol saponin isolated and purified from the total saponin of Panax ginseng leaf. Lu Feng et al. showed that PQDS significantly reduced plasma renin activity, thus blocking the first cascade of RAS response, which may be related to its mechanism of suppressing sympathetic hypertonia and reducing the secretion of large amounts of catecholamines (CA). PQDS can significantly reduce plasma renin activity, suggesting that it can inhibit both sympathetic transmitter and RAS cascade, and break the vicious circle caused by CA and RAS promoting each other, which has a broader effect than angiotensin-converting enzyme inhibitors.
Second, blood-activating and stasis-eliminating drugs
The main effects of blood-activating and stasis-eliminating agents are to promote blood circulation, blood flow and dissipate stasis, which are classified into blood-activating, stasis-eliminating and Y-eliminating agents according to their strengths and weaknesses.
Chuanxiong: Pungent and warm in nature. It belongs to the liver, gall bladder and pericardium meridians. It is effective in activating blood circulation, dispelling wind and relieving pain. Chuanxiong Ligusticum is an active ingredient extracted from the rhizome of Chuanxiong Ligusticum, whose basic chemical structure is tetramethylpyrazine, which has vasodilating, anti-platelet aggregation and calcium antagonistic effects. The effects of Chuanxiong Ligusticum on angiotensin (Ang II), endothelin (ET) and platelet-derived growth factor (PDGF-β) in rats with revascularization were observed by Yinping Sun and others, who showed that after the application of Chuanxiong Ligusticum, the proliferation of common carotid artery vascular smooth muscle cells (VSMC) was reduced, the content of Ang II and ET was significantly decreased and the expression of PDGF-β was significantly weakened. In vitro cell culture revealed that Chuanxiongzin could effectively inhibit the proliferation of angiotensin II-induced vascular smooth muscle cells.
Salvia miltiorrhiza: Bitter and slightly cold in nature. It belongs to the heart, pericardium and liver meridians. It is effective in activating blood circulation and regulating menstruation, removing blood stasis and relieving pain, cooling blood and eliminating carbuncles, and removing annoyance and calming the mind. Xiaoping Gao found that the water-soluble extract of Salvia miltiorrhiza had the strongest inhibitory activity on ACE. In order to screen ACEI from it, the authors extracted water-soluble parts or components of Salvia miltiorrhiza from it, acting on ACE, and identified the ACEI of Salvia miltiorrhiza as salvianolic acid components, mainly salvianolic acid B, rosmarinic acid, and salvinorin by fluorescence assay. It has been confirmed that compound salvia injection can effectively block the ACE activity in the renal tissue of obstructed rats, reduce the production of Ang II, and play a protective role in the kidney.
Safflower: Pungent and warm in nature. It belongs to the heart and liver meridians. It is effective in activating blood circulation, dispelling blood stasis and relieving pain. Its main active ingredients are chalcone pigments and flavonols, and saffron yellow pigment (SY) is the active part group of chalcone, which is a mixture of water-soluble active ingredients in saffron. SY has pharmacological effects such as vasodilatation, antithrombotic, anti-atherosclerosis, hypolipidemic, anti-inflammatory and immunosuppressive. Guo Dengzhou et al. found that compared with the model group, saffron yellow pigment could significantly reduce urinary protein quantification, alleviate renal histopathological damage in rats with diabetic nephropathy, significantly reduce the content of Ang II in renal tissues of rats with diabetic nephropathy (DN), reduce ACE activity in renal tissues of rats with DN, and significantly increase the expression of Ang II protein and genes in renal tissues of rats. It indicates that saffron yellow pigment may maintain the balance of ACE and ACE II by reducing Ang II content, thus regulating the balance of circulation and local vasodilation and contraction, maintaining the stability of renal blood flow and water and salt metabolism, and finally playing a role in antagonizing renal fibrosis.
Turmeric: Pungent, bitter and warm in nature. It belongs to the liver and spleen meridians. Effects: Promoting blood circulation, promoting circulation of Qi, relieving menstrual pain. Curcumin is a biological polyphenol compound extracted from the rhizomes of the plants turmeric, yucca and curcuma longa. It has various pharmacological effects such as anti-inflammatory, antioxidant, hypolipidemic and anti-atherosclerotic. The effect of curcumin on Ang II-induced cardiomyocyte hypertrophy and expression of extracellular signal-regulated kinase (ERK) was investigated using in vitro cultured neonatal rat cardiomyocytes by Bingyan Guo et al. The results showed that Ang II significantly increased the rate of protein synthesis in neonatal rat cardiomyocytes, whereas curcumin significantly inhibited the rate of protein synthesis in cardiomyocytes, indicating that curcumin could inhibit Ang II-induced cardiomyocyte hypertrophy. .
The effect of curcumin is to activate blood circulation and relieve pain; the effect of curcumin is sweet, bitter, and flat, and is classified as a member of the spleen and lung meridians, which is effective in activating blood circulation and stopping bleeding, benefiting qi and consolidating the essence, and nourishing the heart. The combination of the two drugs can benefit Qi and nourish the heart, invigorate blood circulation and promote blood circulation, which can have a synergistic effect. The experimental results confirmed that the “drug pair” of Radix et Rhodiola rosea could improve myocardial remodeling in rats after myocardial infarction, and its mechanism of action might be related to the reduction of Ang II content and AGT mRNA expression in the infarcted myocardial tissue.
Motherwort: Pungent, bitter and slightly cold in nature. Induces the heart, liver and bladder meridians. Its effects include activating blood circulation, regulating menstruation, inducing diuresis, relieving swelling, and clearing heat and detoxification. Motherwort alkaloids are its main active ingredients. Guo Wei et al. experimented with in vitro cultured neonatal rat cardiomyocytes to observe the effect of different concentrations of motherwort hydrastisine on mast cells through Ang II-induced cell hypertrophy and further investigated whether reactive oxygen species (ROS) were involved in its anti-cellular hypertrophy effect. The results showed that Yiwu Cao Shui Sui Sui Lin could inhibit Ang II-induced hypertrophy of neonatal rat cardiomyocytes, and the inhibition of the increase of ROS content might be one of the mechanisms of its action.
Leech: Salty, bitter and flat in nature. Has little toxicity. It belongs to the liver meridian. It is effective in breaking blood circulation, removing blood stasis and eliminating L. Hirudin is its active ingredient. Batller et al. showed that activated human hepatic stellate cells (HSCs) had high expression of angiotensin II type 1 receptor (AT1) using an in vitro study125I Ang II binding assay. It is suggested that activated HSCs are important target organs for AngII in the intrahepatic vascular system, and AngII acting on AT1 receptors in HSCs can cause a significant increase in intracellular calcium, which in turn acts on transcription factors such as AP-1 via ERK and other pathways, ultimately causing HSCs to activate and proliferate. The results of this experiment showed that the percentage change of [ Ca2+ ]i fluorescence intensity of HSCs pretreated with two leech drug serum after Ang Ⅱ stimulation was significantly lower than that of liver fibrosis model control group and normal control group, suggesting that leech blocked or inhibited the Ang Ⅱ signal transduction pathway of HSCs, thus inhibiting the activation and proliferation of HSCs.
Third, heat-clearing drugs
All drugs with the main effect of clearing internal heat can be called heat-clearing drugs, which are classified as heat-clearing and fire-relief, heat-clearing and dampness-drying, heat-clearing and blood-cooling, heat-clearing and detoxification, and heat-clearing and deficiency-heat-clearing according to their concurrent functions. Among these drugs, the more studied RASS antagonists include lotus seed heart, genkoshen, honeysuckle, pelargonium, bitter ginseng and ground bark.
Lotus heart: bitter and cold in nature. It belongs to the heart and kidney meridians. Effects: Clearing the heart and tranquilizing the mind, clearing heat, transporting the heart and kidney, astringing sperm and stopping bleeding. Protohesperidin is a proto-apophorine alkaloid extracted from the green germ of lotus seed heart. Chen Aihua et al. observed the effect of prehesperidin on Ang II-induced apoptosis in human umbilical vein endothelial cells (HUVECs) and found that it significantly enhanced the activity of tNOS, which increased NO secretion from HUVECs, thus antagonizing Ang II-induced endothelial cell apoptosis, and this effect was strongest at a prehesperidin concentration of 1 μmol/L. This effect was strongest at the concentration of 1 μmol/L. It is suggested that low concentration of protopanaxine increases NO secretion from HUVECs by enhancing tNOS activity, especially eNOS activity, and inhibits Ang II-stimulated reactive oxygen species (ROS) production, thus reducing Ang II-induced apoptosis of HUVECs and exerting its function of protecting endothelial cells.
Xuan Shen: Cold in nature, bitter, sweet and salty. It belongs to the lung, stomach and kidney meridians. Rom bousts et al. suggested that ALD may enhance the effect of Ang II in promoting collagen synthesis in cardiac fibroblasts by upregulating the expression of Ang II type 1 receptor (AT1). Xanthopanax can significantly reduce ALD content, which may also be one of the mechanisms of its action to inhibit the increase of Ang II content and thus prevent ventricular remodeling.
Honeysuckle:Sweet and cold in nature. It belongs to the lung, heart and stomach meridians. It is effective in clearing heat and detoxification and dispersing wind-heat. The main active ingredient is chlorogenic acid. From the molecular structure, chlorogenic acid and salvianolic acid B, which can effectively inhibit ACE activity, both have an o-catecholic acid structure, so it is presumed that the o-catecholic acid structure may be the active group for ACE inhibition. Cao Xiaogang et al. screened honeysuckle flowers and active parts that inhibited ACE activity and found that their extracts could inhibit ACE activity. The 70% methanol eluted part of honeysuckle extract inhibited ACE by 87.3% and the main component was chlorogenic acid with a recrystallization purity of 80.4%. Therefore, it is confirmed that honeysuckle extract has strong inhibitory effect on ACE, and the main component of the active site is chlorogenic acid.
Phyllanthus vesiculosus: Sweet, light and slightly cold in nature. It belongs to the heart, liver and gall bladder meridians. It has the effect of clearing heat and detoxifying, diuretic and swelling, draining pus and creating muscle. It contains compounds such as cyanogenic glycosides, flavonoids, sterols and triterpenoids. In addition to its anti-hepatitis and immune activity, it also has ACEI effect and estrogenic effect.Hyuncheol et al. conducted in vitro ACEI effect experiments on various extracted parts of Pendula, and the results showed that the ethyl acetate extracted parts had good activity at 400 μg/ml.Its pharmacology is: Angiotensin-converting enzyme physiologically converts Ang I to Ang II.Ang Ⅱ stimulates Ang II stimulates the synthesis and release of aldosterone from the adrenal cortex, leading to an increase in blood pressure due to Na+ retention. As an angiotensin-converting enzyme inhibitor, the ethyl acetate part of Pterostilbene is mainly used to lower blood pressure by inhibiting angiotensin-converting enzyme and preventing the conversion of Ang I to Ang II.
Bitter ginseng: Bitter and cold in nature. Induces the heart, liver, stomach, large intestine and bladder meridians. It is effective in clearing heat and dampness, killing worms and diuretic. Bitter ginseng alkaloid (Mat) is an alkaloid extracted from bitter ginseng and broad bean root. Its chemical molecular formula is C15H24N2O, which belongs to the tetracyclic quinolizidine group. Experimental study by Yanfang Zhou et al. found that Mat caused fibroblasts (CFs) proliferation to stagnate in the G1 phase and dose-dependently inhibited angiotensin II-induced cardiac fibroblast proliferation. It is suggested that Mat can reverse Ang II-induced myocardial fibrosis by antagonizing the effect of angiotensin II during the formation of myocardial fibrosis.
Digitonin: Cold and sweet in nature. It belongs to the lung, liver and kidney meridians. It has the effect of cooling the blood and removing steam, clearing the lung and lowering fire. The chemical composition has a large number of organic acids such as linoleic acid, linolenic acid, cinnamic acid and two kinds of (s)-9-hydroxy-(10E,12Z)-octadecadienoic acid and (s)-9-hydroxy-(10E,12Z,15Z)-octadecatrienoic acid, which have inhibitory effects on ACE. Zhou Xingwang et al. isolated a white amorphous powder from it, which was identified as octadecyl ferulate by spectroscopy. Pharmacological studies have shown that both the decoction, infusion, tincture and injection of Dictyostelium have significant hypotensive effects on anesthetized dogs, cats, rabbits and rats by intravenous or intramuscular injection or gavage. The realization of its hypotensive effect may be related to the numerous ACE-inhibiting components in ground bark.
Fourth, the cough to relieve phlegm and asthma drugs
Any drug with expectorant or phlegm-eliminating effect is called phlegm-eliminating drug. It is mainly used for cough with phlegm or phlegm and asthma, and the evidence of unpleasant phlegm. At present, there are more researched RASS antagonists, such as maidenhair, antecedent, scapularia, seaweed, etc. Almond is a kind of asthma medicine, which is also described here.
Bayberry:Bitter and cold in nature. It belongs to the lung and heart meridians. It is effective in clearing heat and moistening the lung, relieving cough and resolving phlegm.OH H et al. had found that the inhibition rate of ACE activity by 400 μg/mL of butanol extract of Pimentae pinnatifida was about 59%. Therefore, the biological activity was used as a guide to fractionate three steroidal alkaloids dehydrobezoarine, bezoarine and bezoarine from this extract. The inhibition of ACE activity by these three compounds at concentrations of 15-950 μmol/L was found to be dose-related, with IC50s of 165.0, 312.8 and 26.5 μmol/L, respectively; the IC50 of the positive control drug captopril was 20 nmol/L. This is the first report that steroidal alkaloids have inhibitory effects on ACE.
Qianhu: Bitter, pungent and slightly cold in nature. It belongs to the lung meridian. It is effective in dispersing wind-heat, lowering Qi and resolving phlegm. Pd-Ia is a constituent of Vishnu coumarin extracted from Phyllanthus alba. Wang Ying et al. found that Pd-Ia significantly inhibited Ang II-induced c-Jun protein overexpression in cardiomyocytes, and that elevated intracellular [Ca2+] was an important link in the signal transduction pathway of Ang II-induced hypertrophic response in cardiomyocytes. binding of Ang II to AT1R on the cardiomyocyte membrane activated the cell membrane phospholipase system to produce IP3 and DG, and induced intracellular [ Ca2+] elevation and protein kinase (PKC) activation. PKC activation can initiate nuclear transcription through a series of cascade reactions such as mitogen-activated protein kinase (MAPK). Therefore, it is hypothesized that Pd-Ia may inhibit the intracellular signaling cascade response triggered by Ang II through calcium antagonism, which further inhibits nuclear transcription factors, such as c-Jun protein expression, and thus suppresses cardiomyocyte hypertrophy.
Dracaena scabra: Bitter, pungent and very cold in nature. It belongs to the lung and bladder meridians and has the effects of diarrhea of the lung and lowering of Qi, expectorant and asthma, diuresis and decongestion. Chemical composition is cardiac glycosides, isothiocyanates, fatty oils, etc. Guo Juan et al. found that. In a rat model of ventricular remodeling caused by L-thyroxine sodium (L-Thy), the aqueous extract of D. scabra reduced the amount of Ang II, plasma ALD and myocardial hydroxyproline (Hyp) in myocardial tissue, suggesting that D. scabra aqueous extract has inhibitory effects on RAAS neuroendocrine factor and myocardial This may be one of the mechanisms of myocardial protection and inhibition of myocardial hypertrophy and ventricular remodeling by the aqueous extract of D. scabra.
Seaweed: Salty and cold in nature. It belongs to the liver and kidney meridians. Effects Eliminate phlegm and soften hardness, promote water retention and reduce swelling. The blood pressure-lowering peptide from seaweed is safe, non-toxic and has no side effects, which can lower blood pressure, reduce blood lipids and activate blood vessels. It is a kind of ACE inhibitor, like other protein-derived hypotensive peptides, which inhibits the activity of ACE by competing with the active site of ACE, a zinc-containing dipeptide-complex peptidase with two binding sites for Zn2+, the site of the active group of ACE catalytic reaction. The hypotensive peptide can compete with Zn2+ in the active site of ACE to inactivate ACE, thus preventing ACE from hydrolyzing angiotensin I to angiotensin II and catalyzing hydrolysis of kinin to inactivate the two biochemical reactions, which can have the effect of lowering blood pressure. The ACE inhibitory activity of hypotensive peptide is determined by the molecular mass and amino acid composition structure of the active peptide.
Almond: Bitter and slightly warm in nature. It is slightly toxic. It belongs to the lung and large intestine meridians. It is effective in relieving cough and asthma, laxative and laxative. Almond composition contains amygdalin and fatty oil, protein, various free amino acids. Liu Ning et al. studied the hydrolysis of almond protein powder with Protamex, Alcalase, Neutrase, Flavourzyme, Proleather FG-F and papain respectively, which showed that the hydrolysis products of other proteases, except Flavourzyme, had a good inhibitory effect on ACE, and the concentration of The optimal hydrolysis time of almond protein by Proleather FG-F and Alcalase was 90 min and 180 min, respectively, and the corresponding hydrolysis degree was 16.91% and 18.14%, respectively; the IC50 of the hydrolysates of the two enzymes on ACE was 1.24 mg/ml and 0.98 mg/ml, respectively. After the hydrolysis of amygdalin by Proleather FG-F and Alcalase enzymes, the ACE inhibitory activity was still high after digestion by pepsin and pancreatic enzymes, showing good in vitro digestive stability.
V. Liver pacifying and wind-relieving drugs
Any drug with the effect of pacifying the liver and subduing Yang or relieving wind and spasm is called pacifying and relieving drugs. Mainly used for the treatment of hyperactivity of liver Yang, liver wind within the evidence. At present, the more studied RASS antagonists are hooked vine, antelope horn, flying centipede.
Hooked vine: sweet in taste and slightly cold in nature. It belongs to the liver and pericardium meridians. Effects: Relieving wind and spasm, clearing heat and calming the liver. The main active ingredients of G. crocea are Rhy, Isorhy, etc. Rhy is the main active ingredient of G. crocea, which has the effects of vasodilator, antihypertensive, anti-experimental cerebral ischemia and calcium antagonism. Li Yanju et al. observed the effect of Rhy on the proliferation of Ang II-induced VSMCs by culturing rat vascular smooth muscle cells (VSMCs) and explored the possible mechanism of action. The results showed that Rhy could significantly inhibit the proliferation of Ang II-induced VSMCs in rats in a concentration-dependent manner.
Antelope horn: Salty and cold in nature. It belongs to the liver and heart meridians. It is effective in calming the liver and calming the wind, clearing the liver and clearing the eyes, dispersing blood and detoxifying the toxin. Yang Xingcai observed the efficacy of traditional Chinese medicine Antelope horn in the treatment of hypertension (hyperactivity of liver yang), and the test results showed that the drug has definite antihypertensive efficacy and improves the symptoms of hyperactivity of liver yang, and can reduce the plasma ET-1 and Ang-II levels, improve the function of vascular endothelial cells, increase the NO content, and thus bring the coordination between vasoconstrictor and vasodilator factors into balance. The mechanism of action may be related to its influence on the level of endothelin and nitric oxide, so that the relationship between the two tend to balance.
ALD can promote fibrosis in the heart, lung, kidney and other organs, and is an important pathogenic factor in tissue fibrosis. Therefore, Cui Dajiang et al [29] experimentally observed the effect of Fei Tian Centipede VII on aldosterone in rats with hepatic fibrosis. It was found that serum and liver tissue ALD were significantly higher in the liver fibrosis group compared to the normal control group, which has a pathogenic significance on the formation of liver fibrosis; serum and liver tissue ALD were also elevated in the Feitian Centipede VII group compared to the normal group, probably due to the compensatory increase in ALD as a result of the antagonism of ALD receptors by Feitian Centipede. While Fei Tian Centipede VII mainly exerted its anti-fibrotic effect by antagonizing liver tissue ALD receptors, it had little effect on serum ALD levels.
VI. RASS antagonists of other Chinese medicines
Among other efficacious Chinese medicines, RASS antagonists that have been studied more often include rhubarb, poria, atractylodispersible drug, cangzhu, geranium, dogwood, and garlic, which are used for attacking toxins, killing insects and relieving itching.
Rhubarb: bitter and cold in nature. It belongs to the spleen, stomach, large intestine, liver and pericardium meridians. It is effective in diarrhea and attacking accumulation, clearing heat and fire, cooling the blood and detoxifying the toxin, expelling blood stasis and clearing menstruation. Emodin is an anthraquinone derivative extracted from rhubarb. Yang Yumin et al [30] used rat aortic VSMc cultured in vitro as a model, and Ang II was used to induce VSMc proliferation and establish a cell proliferation model. It was found that rhodopsin at 10-80umol /L could inhibit Ang II-induced VSMc proliferation.
Poria: Sweet, light and flat in nature. It belongs to the heart, spleen and kidney meridians. It is effective in relieving water and swelling, exuding dampness, strengthening the spleen and nourishing the heart. Poriain (Poriatin) is the main active ingredient of Poria. Poriain and aldosterone and its antagonist has a similar structure, can compete for aldosterone receptors on the kidney cell membrane, thus playing anti-aldosterone activity. Deng Gangmin experiments have demonstrated that porin can not only bind to the renal cell membrane aldosterone receptors, but also has anti-aldosterone activity in rats, to improve the urinary sodium to potassium ratio. And has a dose dependent relationship. Porin can compete for aldosterone receptors in vitro, in vivo reversal of aldosterone effect, does not affect the synthesis of aldosterone, these support Porin is a new aldosterone receptor antagonist.
Atractylodes macrocephala: Pungent, bitter and warm in nature. It belongs to the spleen, stomach and liver meridians. It is effective in strengthening the spleen, drying dampness, dispelling wind-dampness, and brightening the eyes. Cang Zhu contains terpenoids, flavonoids, polyene acetylenes and other chemical components. Chen Hongyuan’s experiments proved that the inhibitory effect of Atractylodes macrocephala extract on ACE is obvious and the polarity of the active site is strong, which further enriches the medicinal value of Atractylodes macrocephala, whether its inhibitory activity is the result of single component or multi-component joint action and its mechanism of action is not yet clear.
Lycopodium: Pungent, sweet and flat in nature. It belongs to the lung, spleen and stomach meridians. It is effective in eliminating food and distension, lowering Qi and resolving phlegm. Park Chung-Yun et al. observed the antihypertensive effect of water-soluble alkaloids, the active ingredient of Lycopodium, on spontaneously hypertensive rats (SHR) and found that different doses of Lycopodium significantly increased serum NO levels and decreased plasma Ang II levels in rats, but had no effect on plasma renin activity (PRA). In the group treated with angiotensin type 1 receptor (AT1R) blocker Irbesartan, plasma Ang II levels were significantly increased, indicating that a large amount of Ang II was blocked and failed to bind to AT1R, resulting in relaxation of vascular smooth muscle and a decrease in blood pressure. The experimental results suggest that the antihypertensive effect of water-soluble alkaloids of Lycopodium may be related to the reduction of plasma Ang II level and increase of serum NO level, but not to renin activity and AT1R.
Pueraria lobata: cool in nature, sweet and pungent in taste, belongs to the spleen and stomach meridians, efficacious in relieving symptoms and fever, promoting the production of body fluid, permeating rashes, raising yang and stopping diarrhea. Puerarin is the active part of isoflavones extracted from the dried root of Pueraria lobata, a legume. Sun Wencai et al. observed that Puerarin could cause a significant decrease in plasma endothelin (ET) and Ang II concentrations in patients with atherosclerotic renal artery stenosis (ARAS), presumably by down-regulating ET and Ang II levels and improving insulin resistance, thus playing a role in preventing and treating renal artery stenosis. Puerarin can reduce plasma endothelin, renin activity (RA) and Ang II levels in acute heart attack (AMI) patients within 2 weeks, suggesting that Puerarin has an important role in regulating the disturbed neuroendocrine function in AMI patients. Wang Guoliang et al. found that a certain concentration of AngⅡ could promote VSMC proliferation with an increase in PKC-α and NF-κB expression; a certain concentration of Puerarin could inhibit AngⅡ-induced VSMC proliferation by down-regulating PKC-α and NF-κB expression.
Cornus officinalis:Pungent, bitter, and hot in nature. It is slightly toxic. Induces the liver, spleen, stomach and kidney meridians. It is effective in dispersing cold and relieving pain, lowering rebelliousness and vomiting, and helping Yang to stop diarrhea. Wu Juhua suberine is a monomer extracted from Wu Juhua. Yang Xiaoqing et al. studied the effect of Cornus officinalis on the expression of vasopeptidase C in the thoracic aorta of hypertensive rats. The results showed that angiopeptidase C was effective in reducing blood pressure and improving vascular remodeling, and the mechanism may be related to the inactivation of angiotensin II and activation of kinin release enzyme mediated by the enhanced expression of angiopeptidase C. Ang II concentrations in plasma and thoracic aorta were significantly reduced ( P < 0.05 or P < 0.01) in a dose-dependent manner after wogonin suberin treatment.
Garlic: Pungent and warm in nature. It belongs to the spleen, stomach and lung meridians. It is effective in detoxifying and killing insects, reducing swelling and stopping dysentery. Allicin is the extract of the bulb of garlic from the lily family, which has the effects of lowering blood lipids, anti-inflammatory and anti-tumor. Zhang Dianxin et al. found that allicin could inhibit the proliferation of angiotensin II-induced vascular smooth muscle cells in rabbits, and there were certain dose-dependent and time-responsive relationships.
In summary, Chinese medicine has multi-pathway, multi-target and multi-directional pharmacological characteristics in antagonizing the renin-angiotensin-aldosterone system. The author summarizes and concludes that RASS antagonist herbal medicines have the following characteristics: 1. From the viewpoint of efficacy distribution, they are mainly found in tonic drugs, blood-stasis activating drugs, heat-clearing drugs, phlegm-suppressing drugs, cough-suppressing drugs, liver-suppressing drugs, and other drugs such as antiphlogistic drugs, attacking drugs, diuretic drugs, dampness-permeating drugs, dampness-suppressing drugs, food-eliminating drugs, cold-eliminating drugs, poisoning and insecticidal drugs, etc. They also have individual distribution. There are no such drugs in the medicine of dispelling wind and dampness, rationalizing qi, stopping bleeding, tranquilizing medicine, astringent medicine, anthelmintic medicine, orifice opening medicine, vomiting medicine, and plucking poison and muscle growth medicine. 2. From the medicinal properties of drugs, there are 18 cold medicines, 11 hot medicines, and 4 flat medicines. There are 12 flavors in Hand Shao Yin Heart meridian, 10 flavors in Hand Tai Yin Lung meridian, 9 flavors in Foot Tai Yin Spleen meridian, and 8 flavors in Foot Yang Ming Stomach meridian.
RASS antagonistic herbal medicines are an important source of innovative drugs because of their wide source, low toxicity, low cost and rich structure types of compounds. By extracting RASS-antagonizing active ingredients from natural drugs and using them in combination with western drugs according to patients’ different types of evidence and symptoms, the adverse effects of western drugs can be reduced. Moreover, in view of the long-term use of drugs for hypertension and other diseases, it is of great practical significance to develop highly effective and low-toxic drugs with independent patents to antagonize the renin angiotensin system.