{"id":59253,"date":"2024-06-25T10:30:02","date_gmt":"2024-06-25T10:30:02","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=59253"},"modified":"2024-07-03T17:49:06","modified_gmt":"2024-07-03T17:49:06","slug":"the-antihypertensive-effect-of-marchin-13-tang-on-l-name-induced-hypertension-in-rats","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/the-antihypertensive-effect-of-marchin-13-tang-on-l-name-induced-hypertension-in-rats\/","title":{"rendered":"The Antihypertensive Effect of Marchin-13 Tang on L-NAME-induced Hypertension in Rats"},"content":{"rendered":"\n

Introduction <\/strong><\/p>\n\n\n\n

The World Health Organization (WHO)\nhas conveyed that around 1.28 billion adults across the globe experience\nhypertension1<\/sup>. In\nMongolia, hypertension accounts for 50% of all cardiovascular ailments, making\nit the leading cause of mortality. This underscores the significant public\nhealth issue posed by hypertension in Mongolia, where it contributes to one of\nthe world’s highest rates of death from hemorrhagic stroke2,3<\/sup>. Arterial hypertension is often treated with modern\npharmaceuticals, but these medications usually lead to various side effects4<\/sup>.\n The\nWHO reports a rising trend in using herbal medicines in primary healthcare\nwithin developing countries, home to approximately 70 to 80 percent of the\nworld’s population5<\/sup>. Consequently, there is a growing interest in\nresearching inexpensive herbal medicines with few side effects6,7<\/sup>. Numerous traditional medicinal Tangs have\nbeen utilized in the treatment of hypertensive disease.According to\nresearch by Bin Dai, the traditional Chinese medicine Gao Zhi Yao contains\nherbs with various medicinal properties and can lower blood pressure and\nrestore the cardiovascular system by nitric oxide (NO) and angiotensin II (Ang\nII) in the hypertension model8<\/sup>.<\/p>\n\n\n\n

In traditional Mongolian medicine, Marchin-13 (M-13) Tang is used for treatment and has a history of use in traditional medicine for treating symptoms such as high blood pressure, stiff neck, and headaches9<\/sup>. Despite this, its effect action, and chemical composition have not been studied. Therefore, evaluating the antihypertensive effects of Marchin-13 Tang is important for further use in clinical practice.  The M-13 Tang comprises C. tinctorius<\/em> L, S. manshurica<\/em> L, Fructus G. jasminoides<\/em> J, R. cordifolia<\/em> L, Trollius asiaticus <\/em>L, Quercus robur <\/em>L, Z. officinale<\/em> Roscoe, P. incarnata <\/em>(DC.) Freyn, Fructus T. bellirica<\/em> Roxb, Radix I. helenium<\/em> L, Radix S. alopecuroides<\/em> L, Fructus T. chebula<\/em> Retz, and A. guttata<\/em> Bunge9<\/sup>. The pharmacological effects of these components are anti-inflammatory, antioxidant, neuroprotective, and antihypertensive. For example, the C. tinctorius<\/em> L extract exhibits antihypertensive effects in hypertensive models induced by L-NAME10<\/sup>. The compound aloperine in S. alopecuroides<\/em> L can improve nervous system function and lower blood pressure while exhibiting anti-inflammatory, pain-relieving, soothing, anti-tumor, and antibacterial properties11<\/sup>. Inula helenium<\/em> L demonstrated anti-inflammatory, antioxidant, neuroprotective, and antiproliferative effects on cancer cell lines including antibacterial, antifungal, and prebiotic properties12<\/sup>. <\/p>\n\n\n\n

N(gamma)-nitro-L-arginine\nmethyl ester (L-NAME) is commonly utilized internationally to induce a\npathological model of hypertension in experimental animals, leading to a\ndecrease in the production of nitric oxide (NO)13<\/sup>.\nThe development of hypertension has been linked to\noxidative stress, as evidenced by heightened levels of lipid peroxidation in\nindividuals with high blood pressure. The surge in oxidative stress is known to\ndiminish the availability of NO, a potent vasodilator, contributing to the onset of\nhypertension14<\/sup>. L-NAME causes an increase in angiotensin-converting\nenzyme (ACE) activity, and this elevated ACE activity subsequently promotes the\ntransformation of Ang I (Angiotensin I) to Ang II (Angiotensin II). Angiotensin\nII (Ang II) directly causes constriction of blood vessels, resulting in\nincreased blood pressure15<\/sup>. <\/p>\n\n\n\n

Consequently,\nthis research aims to assess the impact of Marchin-13 Tang on ACE activity, NO\nlevels, antioxidant enzyme function, and malondialdehyde (MDA) in rats with\nhypertension induced by L-NAME. Captopril was used in the study as a positive\ncontrol due to its ACE-inhibitory properties. <\/p>\n\n\n\n

Materials and methods<\/strong><\/strong><\/p>\n\n\n\n

Reagent<\/strong> <\/strong>and Drugs<\/strong> <\/p>\n\n\n\n

N(gamma)-nitro-L-arginine\nmethyl ester Hydrochloride (L-NAME, N0661; EC No. 257-116-1) and reference of\ngallic acid, rutin was picked up from Sigma-Aldrich Co.,(USA). Enzyme-linked immune sorbent assay (ELISA) kits\npurchased from MLBio Co. (China) were used in the study. The Marchin-13\nTang (serial number 951017), was purchased\nfrom the traditional pharmacy of the Institute of Traditional Medicine and Technology\n(ITMT) of Mongolia. Captopril (No:\n10722A, Sopharma, Bulgaria) was purchased from a pharmacy in Ulaanbaatar,\nMongolia.<\/p>\n\n\n\n

Animals <\/strong><\/p>\n\n\n\n

We\nobtained 50\nhealthy male Wistar rats weighing between 210 and 250 grams from the\nexperimental animal center at the ITMT of Mongolia. These rats were\naccommodated in controlled environment conditions: temperature at 20\u00b11\u00b0C,\nhumidity at 50-60%, a 12-hour light\/dark cycle was established, and automatic\nventilation was provided 8-15 times per hour. They were supplied with standard\nnutrients and water ad libitum. <\/p>\n\n\n\n

Ethical\nStatement<\/strong><\/p>\n\n\n\n

We conducted the\nstudy per the animal experiment guidelines after obtaining approval from the\nMNUMS Ethics Committee (permit \u21162021\/3-06). <\/p>\n\n\n\n

Chemical analysis<\/strong><\/p>\n\n\n\n

Sample preparation<\/strong><\/p>\n\n\n\n

1 g of the powder of M-13 Tang was precisely weighed and extracted with 100 mL of 70% ethanol for 20 minutes at 700<\/sup>C, then cooled and filtered (Solution A).<\/p>\n\n\n\n

Estimation of total flavonoid contents<\/strong><\/p>\n\n\n\n

3 mL of solution A was mixed with 6 mL of distilled H2O and 1 mL NaNO2 (5%\u2009w\/v in water), shaken for 6 minutes, and 1 mL of 10% Al (NO3)3. After 6 minutes, 10 mL of 4% HCL was added and diluted up to 25 mL with distilled H2O, kept at room temperature for 15 min16<\/sup>. The absorbance was determined using Ultraviolet-visible Spectrophotometry at 500. Rutin equivalent was represented as the value of total flavonoids suggested in the M-13 Tang17<\/sup>. <\/p>\n\n\n\n

Quantification of total phenolic compounds<\/strong><\/p>\n\n\n\n

The assessment of total phenolic compound content was conducted employing the Folin-Ciocalteu reagent16<\/sup>. Solution A had 99.6 mL of water added to it (Solution B). 10 mL of Solution B was mixed with 1 mL of 10% aqueous Folin-Ciocalteu solution and 14 ml aqueous Na2CO3 solution (10.75%\u2009w\/v in water) stirred and left for 40 min.  The absorbance value was measured in the test solution at 760 nm using a UV spectrophotometer (UV\/VIS, Italy). The gallic acid equivalent was used to represent the content of the polyphenolic compound found in the M-13 Tang18<\/sup>.<\/p>\n\n\n\n

Preparation\nof Marchin-13 Tang<\/strong><\/p>\n\n\n\n

Marchin-13 Tang\nwas purchased from the traditional pharmacy of the Mongolian ITMT (Ulaanbaatar,\nMongolia). The composition of the raw materials of Marchin-13 Tang is shown in\nTable 1. The decoction was prepared as a water extract with a concentration of\n1:10 of M-13 powder according to the instructions of the National Pharmacopoeia\nof Mongolia (2011)19<\/sup>. <\/p>\n\n\n\n

Table 1: Composition of M-13 Tang<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Latin name<\/strong><\/p>\n<\/td>\n

\n

Amount (g)<\/strong><\/p>\n<\/td>\n

\n

Herb part<\/strong><\/p>\n<\/td>\n

\n

Pharmacological effects<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Carthamus tinctorius<\/em> L<\/p>\n<\/td>\n

\n

0.130<\/p>\n<\/td>\n

\n

Herb<\/p>\n<\/td>\n

\n

Antihypertensive, antioxidant, anti-inflammatory and cardioprotective20<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Sambucus manshurica <\/em>L<\/p>\n<\/td>\n

\n

0.210<\/p>\n<\/td>\n

\n

Caulis<\/p>\n<\/td>\n

\n

Antihypertensive, antioxidant, antimicrobial, antidiabetic, anti-inflammatory and antidepressant21<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Gardenia jasminoides <\/em>J. Ellis<\/p>\n<\/td>\n

\n

0.086<\/p>\n<\/td>\n

\n

Fructus<\/p>\n<\/td>\n

\n

Antihyperglycemic, anti-atherosclerotic, anti-inflammatory, anti-arthritis, anti-apoptotic, antioxidant, anti-angiogenic, and antithrombotic22<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Rubia cordifolia <\/em>L<\/p>\n<\/td>\n

\n

0.080<\/p>\n<\/td>\n

\n

Radix and rhizoma<\/p>\n<\/td>\n

\n

antibacterial, antioxidant, anticancer, anti-inflammatory, analgesic and hepatoprotective23<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Trollius asiaticus <\/em>L<\/p>\n<\/td>\n

\n

0.064<\/p>\n<\/td>\n

\n

Herb<\/p>\n<\/td>\n

\n

Antiviral, antibacterial, anti-inflammatory and antioxidant24<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Quercus robur <\/em>L<\/p>\n<\/td>\n

\n

0.064<\/p>\n<\/td>\n

\n

Fructus<\/p>\n<\/td>\n

\n

Antioxidant, antibacterial, antifungal, antidiabetic25<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Z. officinale<\/em> Roscoe<\/p>\n<\/td>\n

\n

0.064<\/p>\n<\/td>\n

\n

Radix<\/p>\n<\/td>\n

\n

Antioxidant, anti-inflammatory, a blocker of voltage-dependent Ca2+ channels, a regulator of endothelial dysfunction and NO synthesis, an inhibitor of angiogenesis26<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Pyrola incarnata <\/em>(DC.) Freyn<\/p>\n<\/td>\n

\n

0.061<\/p>\n<\/td>\n

\n

Folium<\/p>\n<\/td>\n

\n

Antioxidant27<\/sup>, Antimicrobial28<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Terminalia bellirica <\/em>(Gaertn.) Roxb<\/p>\n<\/td>\n

\n

0.061<\/p>\n<\/td>\n

\n

Fructus<\/p>\n<\/td>\n

\n

Antihypertensive, Ca++ antagonist2<\/sup>9<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Inula helenium <\/em>L<\/p>\n<\/td>\n

\n

0.052<\/p>\n<\/td>\n

\n

Radix<\/p>\n<\/td>\n

\n

Anti-inflammatory, antioxidant, neuroprotective, antiproliferative3<\/sup>0<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Sophora alopecuroides <\/em>L<\/p>\n<\/td>\n

\n

0.049<\/p>\n<\/td>\n

\n

Radix<\/p>\n<\/td>\n

\n

Antihypertensive, anti-inflammatory, pain-relieving, soothing, anti-tumor, and antibacterial properties31<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Terminalia chebula<\/em> Retz<\/p>\n<\/td>\n

\n

0.049<\/p>\n<\/td>\n

\n

Fructus<\/p>\n<\/td>\n

\n

Antihypertensive, ACE inhibitor32<\/sup>, antioxidant, anti-in\ufb02ammatory, hepatoprotective, nephroprotective, antibacterial33<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Arnebia guttata <\/em>Bunge<\/p>\n<\/td>\n

\n

0.042<\/p>\n<\/td>\n

\n

Radix<\/p>\n<\/td>\n

\n

Antibacterial, anti-inflammatory, hepatoprotective, antiviral34<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Experimental\nProtocols<\/strong><\/strong><\/p>\n\n\n\n

The experimental\nprotocols involved randomizing the animals into five groups comprising 10 rats\nand subjecting them to various treatments over 21 days. <\/p>\n\n\n\n

Group I served as the control and received distilled water orally. <\/p>\n\n\n\n

Group II the hypertensive control, received L-NAME orally at 40 mg\/kg\/day35<\/sup>.<\/p>\n\n\n\n

Group III received Captopril orally at 5 mg\/kg\/day35<\/sup> and\nL-NAME at 40 mg\/kg\/day.<\/p>\n\n\n\n

Group IV received oral administration of M-13 Tang at 90 mg\/kg\/day doses\nand L-NAME at 40 mg\/kg\/day. <\/p>\n\n\n\n

Group IV received oral administration of M-13 Tang at 180 mg\/kg\/day doses\nand L-NAME at 40 mg\/kg\/day. <\/p>\n\n\n\n

We assessed rat systolic and diastolic blood pressure using tail-cuff sensors on days 0, 7, 14, and 21. <\/strong><\/p>\n\n\n\n

Measurement\nof Systolic<\/strong> <\/strong>and Diastolic Blood\nPressure<\/strong><\/p>\n\n\n\n

Noninvasive\nblood pressure measurements were conducted using a tail cuff on the rat’s tail.\n(Systole, Neurobotics, LLC, Moscow, Zelenograd). To perform noninvasive blood\npressure measurements in rats, the animals were initially pre-warmed to a\ntemperature of 28-32 degrees Celsius for 10-15 minutes. This step ensures\nadequate blood circulation in the tail and stabilizes blood flow36<\/sup>.\nA Phlogiston heating platform was utilized for heating (Phlogiston platform, Neurobotics, LLC, Moscow, Zelenograd)37<\/sup>. The Daniel\nDeMers method calculated the mean arterial pressure (MAP)38<\/sup>. <\/p>\n\n\n\n

Enzyme-linked\nImmune sorbent assay (ELISA)<\/strong><\/p>\n\n\n\n

We collected\nblood samples 21 days later, let them stand for 15 minutes at room temperature,\nand then centrifuged them at 3000 rpm for 10 minutes to separate the serum. We\nmeasured the levels of  Rat SOD (superoxide\ndismutase, sensitivity: 0.1 pg\/ml), Rat CAT (catalase, sensitivity: 0.1 ng\/L), Rat\nNO (nitric oxide, sensitivity: 0.1 \u03bcmol\/L), Rat ACE (angiotensin converter\nenzyme, sensitivity: 0.1 ng\/L), and Rat MDA (malondialdehyde, sensitivity: 0.01\nnmol\/L) using ELISA kits (Shanghai MLBIO Biotechnology Co.). According to the\nmanufacturer’s instructions, an ELISA kit is made using a microplate reader\n(ChroMate-4300, Awareness Technology Co., USA).   <\/p>\n\n\n\n

Statistical analysis<\/strong><\/p>\n\n\n\n

The mean and\nstandard deviation (SD) were computed for the observed values within each\ngroup, and the analysis used GraphPad Prism-9 software. A nonparametric\nKruskal-Wallis test was used for the statistical analysis. The significance\nlevel was p < 0.05.<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

Polyphenolic compound and flavonoid contents <\/strong><\/p>\n\n\n\n

The polyphenolic compounds content of the ethanolic\nextract in M-13 Tang measured from the regression equation of calibration curve\n(y=0.084x \u2013 0.001, r\u00b2 =0.999) were 29.6\u00b10.16 mg\/g. The\ncontent of flavonoids in the ethanolic extract of M-13 tang, in rutin\nequivalent, measured using the calibration curve’s regression equation\n(y=0.041x + 0.007, r2 =0.9911) and are being represented in RuE were 18.1\u00b10.1 mg\/g. (Table\n2). <\/p>\n\n\n\n

Table 2: Polyphenolic and flavonoids in ethanol extract of the M-13 Tang<\/strong><\/p>\n\n\n\n\n\n\n\n
\n

\u2116<\/strong><\/p>\n<\/td>\n

\n

Bioactive compounds of M-13 Tang<\/strong><\/p>\n<\/td>\n

\n

Standard<\/strong><\/p>\n

reagent<\/strong><\/p>\n<\/td>\n

\n

Content (mg\/g)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.<\/p>\n<\/td>\n

\n

Total flavonoids<\/p>\n<\/td>\n

\n

Rutin<\/p>\n<\/td>\n

\n

18.1\u00b10.1 mg\/g<\/p>\n<\/td>\n<\/tr>\n

\n

2.<\/p>\n<\/td>\n

\n

Polyphenolic compounds<\/p>\n<\/td>\n

\n

Gallic acid<\/p>\n<\/td>\n

\n

29.6\u00b10.16 mg\/g<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Effects\nof M-13 Tang on blood pressure in hypertensive model<\/strong><\/p>\n\n\n\n

No significant differences were observed in MAP values\namong the five groups under investigation at the study’s commencement. However,\nfrom days 7 to 21, a notable increase in MAP was evident in the L-NAME group\ncompared to the control group. In the comparative analysis, the group\nadministered Captopril demonstrated significant reductions in MAP on days 7,\n14, and 21 (p<0.01). Additionally, the administration of M-13 Tang (90\nmg\/kg and 180 mg\/kg) significantly reduced MAP on days 14-21 (p<0.01) (Fig. 1).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: MAP in L-NAME induced hypertensive model<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

SBP and DBP exhibited a significant increase in the L-NAME group compared to the control group (p<0.01). Animals treated with Captopril and M-13 Tang showed a substantially reduced SBP and DBP compared to the L-NAME group (p<0.01) (Tables 3 and 4).<\/p>\n\n\n\n

Table 3: SBP in L-NAME induced hypertensive model<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
\n

Time Point<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n

(mmHg)<\/strong><\/p>\n<\/td>\n

\n

L-NAME<\/strong><\/p>\n

(mmHg)<\/strong><\/p>\n<\/td>\n

\n

Captopril <\/strong><\/p>\n

5 mg\/kg (mmHg) <\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

90 mg\/kg (mmHg)<\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

180 mg\/kg (mmHg)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0 day<\/p>\n<\/td>\n

\n

115.2\u00b15.15<\/p>\n<\/td>\n

\n

117.1\u00b16.43<\/p>\n<\/td>\n

\n

123.8\u00b13.71<\/p>\n<\/td>\n

\n

121.0\u00b13.03<\/p>\n<\/td>\n

\n

127.8\u00b14.35<\/p>\n<\/td>\n<\/tr>\n

\n

7 days<\/p>\n<\/td>\n

\n

95.6\u00b14.31<\/p>\n<\/td>\n

\n

142.5\u00b16.93##<\/sup><\/p>\n<\/td>\n

\n

109.5\u00b19.05*<\/sup><\/p>\n<\/td>\n

\n

133.0\u00b16.48<\/p>\n<\/td>\n

\n

126.6\u00b16.40<\/p>\n<\/td>\n<\/tr>\n

\n

14 days<\/p>\n<\/td>\n

\n

105.6\u00b16.65<\/p>\n<\/td>\n

\n

171.7\u00b17.96##<\/sup><\/p>\n<\/td>\n

\n

118.0\u00b19.96**<\/sup><\/p>\n<\/td>\n

\n

120.6\u00b111.4**<\/sup><\/p>\n<\/td>\n

\n

112.1\u00b19.92**<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

21 days<\/p>\n<\/td>\n

\n

114.4\u00b14.99<\/p>\n<\/td>\n

\n

166.2\u00b19.42##<\/sup><\/p>\n<\/td>\n

\n

112.7\u00b16.74**<\/sup><\/p>\n<\/td>\n

\n

116.0\u00b18.65**<\/sup><\/p>\n<\/td>\n

\n

113.6\u00b110.1**<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Results are expressed as mean \u00b1 SD (n=8). ##p < 0.01, L-NAME group vs. control group; *p < 0.05, **p < 0.01, Captopril 5 mg\/kg, M-13 90 mg\/kg and M-13 180 mg\/kg group vs. L-NAME group.<\/p>\n\n\n

Table 4: DBP in L-NAME induced hypertensive rats<\/strong> <\/p>\n\n\n\n\n\n\n\n\n\n
\n

Time Point<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n

(mmHg)<\/strong><\/p>\n<\/td>\n

\n

L-NAME<\/strong><\/p>\n

(mmHg)<\/strong><\/p>\n<\/td>\n

\n

Captopril <\/strong><\/p>\n

5 mg\/kg (mmHg) <\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

90 mg\/kg (mmHg)<\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

180 mg\/kg (mmHg)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0 day<\/p>\n<\/td>\n

\n

75.2\u00b16.71<\/p>\n<\/td>\n

\n

64.2\u00b15.50<\/p>\n<\/td>\n

\n

73.6\u00b18.50<\/p>\n<\/td>\n

\n

74.4\u00b18.14<\/p>\n<\/td>\n

\n

73.6\u00b16.44<\/p>\n<\/td>\n<\/tr>\n

\n

7 days<\/p>\n<\/td>\n

\n

76.6\u00b15.08<\/p>\n<\/td>\n

\n

118.1\u00b16.39##<\/sup><\/p>\n<\/td>\n

\n

76.5\u00b19.50*<\/sup><\/p>\n<\/td>\n

\n

88.3\u00b112.2<\/p>\n<\/td>\n

\n

104.6\u00b18.74<\/p>\n<\/td>\n<\/tr>\n

\n

14 days<\/p>\n<\/td>\n

\n

74.4\u00b14.86<\/p>\n<\/td>\n

\n

133.1\u00b19.27##<\/sup><\/p>\n<\/td>\n

\n

85.0\u00b111.94**<\/sup><\/p>\n<\/td>\n

\n

89.6\u00b110.1**<\/sup><\/p>\n<\/td>\n

\n

74.0\u00b19.05**<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

21 days<\/p>\n<\/td>\n

\n

73.6\u00b13.85<\/p>\n<\/td>\n

\n

136.6\u00b17.58##<\/sup><\/p>\n<\/td>\n

\n

83.1\u00b18.20**<\/sup><\/p>\n<\/td>\n

\n

90.5\u00b15.0**<\/sup><\/p>\n<\/td>\n

\n

88.6\u00b111.9**<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Results are expressed as mean \u00b1 SD (n=8). ##p < 0.01, L-NAME group vs. control group; *p < 0.05, **p < 0.01, Captopril 5 mg\/kg, M-13 90 mg\/kg and M-13 180 mg\/kg group vs. L-NAME group.<\/p>\n\n\n

Effect of M-13 Tang on serum of NO levels in L-NAME-induced hypertensive model<\/strong><\/p>\n\n\n\n

NO synthesis was inhibited in the L-NAME-induced hypertension model. The captopril (5 mg\/kg) group and the M-13 Tang (90 mg\/kg) group exhibited significant increases in serum NO levels compared to the L-NAME group (p<0.05). There was a dose-dependent restoration of NO in the serum of the M-13 Tang groups (Figure 2).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Levels of serum NO <\/strong>in L-NAME-induced hypertension model<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Effect of M-13 Tang on serum of ACE activity in L-NAME-induced hypertensive model<\/strong><\/p>\n\n\n\n

A significant increase in serum ACE levels was observed in the L-NAME group compared to the normal control group (p<0.05). Conversely, the ACE level exhibited a significant reduction in both the Captopril and M-13 Tang (90 mg\/kg) treated groups compared to the L-NAME group (p<0.05). There was a dose-dependent reduction of ACE in the serum of the M-13 Tang groups (Figure 3).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3: Levels of serum ACE <\/strong>in L-NAME-induced hypertension model<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Effects of M-13 Tang on serum of MDA and antioxidant enzyme levels<\/strong><\/p>\n\n\n\n

Table 4 shows the concentrations\nof MDA, SOD, and CAT in the serum of the experimental groups. L-NAME administration in rats significantly increased\nthe level of MDA (a marker of oxidative stress) compared with control rats (p<0.05). However, when administered to hypertensive rats,\ncaptopril and M-13 Tang (90 and 180 mg\/kg) significantly decreased MDA levels,\nindicating a reduction in L-NAME-induced oxidative stress. Furthermore, we observed that L-NAME markedly\ndiminished the antioxidant enzymes SOD and CAT, indicating oxidative stress\ncompared to the control group (p<0.01). Treatment with M-13 (90 and 180\nmg\/kg) notably decreased oxidative stress by restoring the beneficial\nantioxidant enzymes SOD and CAT (p<0.01).<\/p>\n\n\n\n

Table 4: Levels of serum MDA and antioxidant enzymes in L-NAME-induced hypertension<\/strong><\/p>\n\n\n\n\n\n\n\n\n
\n

Parameter<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

L-NAME<\/strong><\/p>\n<\/td>\n

\n

Captopril<\/strong><\/p>\n

(5 mg\/kg)<\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

(90 mg\/kg)<\/strong><\/p>\n<\/td>\n

\n

M-13<\/strong><\/p>\n

(180 mg\/kg)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

MDA (nmol\/L)<\/p>\n<\/td>\n

\n

11.11\u00b14.50<\/p>\n<\/td>\n

\n

24.44 \u00b1 5.77#<\/sup><\/p>\n<\/td>\n

\n

16.52 \u00b1 2.51*<\/sup><\/p>\n<\/td>\n

\n

15.13 \u00b1 4.53*<\/sup><\/p>\n<\/td>\n

\n

16.44 \u00b1 5.00*<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

SOD (pg\/ml)<\/p>\n<\/td>\n

\n

99.60\u00b111.8<\/p>\n<\/td>\n

\n

39.64 \u00b1 6.58##<\/sup><\/p>\n<\/td>\n

\n

78.27 \u00b1 8.16**<\/sup><\/p>\n<\/td>\n

\n

62.36 \u00b1 7.45**<\/sup><\/p>\n<\/td>\n

\n

66.53 \u00b1 8.42**<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

CAT (ng\/L)<\/p>\n<\/td>\n

\n

41.80\u00b16.33<\/p>\n<\/td>\n

\n

21.67 \u00b1 2.12##<\/sup><\/p>\n<\/td>\n

\n

35.56 \u00b1 7.91*<\/sup><\/p>\n<\/td>\n

\n

33.53 \u00b1 3.93*<\/sup><\/p>\n<\/td>\n

\n

32.21 \u00b1 5.54*<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Results are expressed as mean \u00b1 SD (n=6). #p<0.05, ##p < 0.01, L-NAME group vs. control group; *p < 0.05, **p < 0.01, Captopril 5 mg\/kg, M-13 90 mg\/kg and M-13 180 mg\/kg group vs. L-NAME group.<\/p>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

Marchin-13 Tang is a\ntraditional drug widely used in Mongolian traditional medicine to reduce blood pressure.\nAn acute toxicity study of M-13 Tang, conducted using the by express method of\nProzorovskii V.B39<\/sup> determined the median lethal dose (LD50) to be\n4.47 g\/kg. Therefore, we selected 90 mg\/kg and 180 mg\/kg doses for this study. This\nstudy demonstrated the first experimental investigation to assess whether M-13\nTang exhibits an antihypertensive effect in L-NAME-induced hypertensive rat\nmodels. We observed that administering M-13 Tang in L-NAME-induced hypertensive\nrats reduced blood pressure and exerted antioxidant effects.<\/p>\n\n\n\n

L-NAME is a synthetic substance that\ninhibits NO, and it is widely used internationally to create a model of\nhypertension in experimental animals13,40,41<\/sup>. NO produced by\nvascular endothelial cells is a potent vasodilator and plays an important role\nin vascular resistance and growth42<\/sup>. In this study, we found that\nadministration of M-13 Tang (90 mg\/kg) reduced blood pressure through\nvasodilation by restoring inhibited NO production. Campbell\u2019s\nstudy reported increased oxidative stress, vascular inflammation, ACE activity,\nand expression following L-NAME administration13<\/sup>. ACE, pivotal in\nthe RAAS, converts angiotensin I to angiotensin II, which is crucial in\nregulating blood pressure and fluid balance. Angiotensin II promotes\nvasoconstriction, leading to an increase in blood pressure14,15<\/sup>. In\nthe current study, M-13 Tang (90 mg\/kg) reduced serum ACE activity in rats receiving L-NAME. It was nearly as\neffective as the positive control captopril. Captopril inhibits the conversion\nof angiotensin I to angiotensin II, thereby reducing the processes that lead to\nhigh blood pressure and heart failure43<\/sup>. Captopril has been reported\nto have antioxidant properties with its thiol group44<\/sup> and is widely\nused in clinical practice. <\/p>\n\n\n\n

The M-13 Tang contains several herbs with antihypertensive\nproperties. For instance, C<\/em>.<\/em> tinctorius <\/em>L normalized the renin-angiotensin system (RAS), NO\nbioactivity, reduced oxidative stress markers, and improved endothelial\nfunction in L-NAME-induced hypertensive rats10<\/sup>. Manuela Ciocoiu’s study\nalso demonstrated that the polyphenolic extract of S. manshurica<\/em> L\nreduced SBP and DBP in the hypertension model45<\/sup>. Crocetin, a biologically active substance in G<\/em>.<\/em> jasminoides<\/em> J, possesses antihypertensive and antithrombotic\neffects, prevents insulin resistance, and enhances sleep quality46<\/sup>.\nAlso, there have been reports of the ACE activity inhibitory effects of Z<\/em>.<\/em> officinale<\/em> Roscoe15<\/sup>. It has been utilized in traditional\nmedicine to address hypertension and various cardiovascular ailments47<\/sup>.\n<\/p>\n\n\n\n

This\nstudy demonstrates that L-NAME elevated serum lipid peroxidation\ndecreased the level of antioxidant enzymes SOD, and CAT compared to the control\ngroup leading to\nsevere tissue damage. This data is consistent with the results of other studies that L-NAME inhibits the activity of SOD and CAT48<\/sup>\nwhereas increases MDA in serum49<\/sup> causing hypertension in rats.  According to Harrison\u2019s\nstudy, oxidative\ndamage worsens as blood pressure increases49<\/sup>. <\/p>\n\n\n\n

We found that M-13 Tang\nat a dose of 90 and 180 mg\/kg reduced the serum MDA level compared to the\nL-NAME-induced hypertension group, indicating a protective effect against\nL-NAME-induced oxidative damage of vascular tissue. Moreover, M-13 Tang at a\ndose of 90 mg\/kg increased significantly the levels of the antioxidant enzymes SOD and CAT\ncompared to L-NAME\ninduced hypertension group. These data indicate that\nM-13 Tang\npossesses antioxidant activity.<\/p>\n\n\n\n

Our chemical analysis\ndetermined that M-13 Tang contains total phenolic (gallic acid 29.6\u00b10.16 mg\/g),\nand flavonoids (rutin, 18.1\u00b10.1 mg\/g). We hypothesize that this antioxidant\nactivity is\nrelated to the high-content polyphenols of M-13 Tang.\nResearchers have discovered that phenolic and flavonoid compounds display\nanti-inflammatory50<\/sup>, antibacterial, and antioxidant effects, along\nwith biologically active properties that help reduce blood pressure51<\/sup>\nand decrease edema. Gallic acid demonstrates diuretic, anti-inflammatory, and\nsoothing effects52<\/sup>. Li Jin and Xiao Yan’s study showed that gallic\nacid modulates the components of the renin-angiotensin-aldosterone system (RAAS),\nleading to a decrease in the expression of Ang II type I receptor (AT1) and angiotensin-converting\nenzyme inhibitor (ACEI) proteins within the aorta. Additionally, gallic acid\nrelaxes vasoconstriction in both the aorta and mesenteric arteries and has been\nstudied for antihypertensive effects53,54<\/sup>. <\/p>\n\n\n\n

In the current study, M-13 Tang inhibited L-NAME induced serum ACE\nactivity  in rats . Also, our\nstudy demonstrated that treatment with M-13 Tang prevented the decrease in serum NO\ninduced by L-NAME. Hence, M-13 Tang\n(90 and 180 mg\/kg) showed\nantihypertensive effects\nagainst L-NAME induced hypertension in rats. There\nare many studies on antihypertensive traditional Chinese medicine. For example,\nGAO-ZI-YAO Tang has the effect of reducing blood pressure and restoring the\ncardiovascular system by regulating the production of NO and Ang II, as well as\nreducing inflammation8<\/sup>.<\/p>\n\n\n\n

A limitation of our study is that we used only one model\nof hypertension. Further studies are also needed to isolate the biologically\nactive substances of Marchin-13 Tang and investigate its antihypertensive\neffect in other models of hypertension. It would help to give more\nunderstanding of the mechanism of M-13 Tang. \n<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

In conclusion, we found that Marchin-13 Tang,\nsignificantly reduced MDA and ACE levels, while increasing NO, SOD, and CAT\nactivities compared to L-NAME induced hypertension in rats. Consequently, these\ndata indicate that the antioxidant activity of Marchin-13 Tang plays a crucial\nrole in the antihypertension effect. We are pioneering the investigation into\nthe antihypertensive effects of Marchin-13 Tang.  <\/p>\n\n\n\n

Acknowledgments<\/strong><\/p>\n\n\n\n

We\nthank the Institute of Traditional Medicine and Technology’s Research Center and\nthe project team for their support during this study. <\/p>\n\n\n\n

Conflict\nof Interest <\/strong><\/p>\n\n\n\n

The\nauthors declare that they have no conflict of interest.<\/p>\n\n\n\n

Funding\nSource<\/strong><\/p>\n\n\n\n

Foundation of Science and Technology,\nMongolia, Grant\/Award number: Shut\/Z-2017\/05<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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