This work was supported by the National Natural Science Foundation of Jilin Province (no. YDZJ202301ZYTS189).

All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Changchun University of Chinese Medicine. The materials are listed in the Table of Materials.
1. Animals and treatment
<ol>
	<li>Randomly divide a total of 50 adult spontaneously hypertensive rats (SHRs) (male, 50 days old) into five groups, including control (CON), methionine (MET), MET + HTJDTLD + Enalapril maleate (EM), MET + EM, and MET + HTJDTLD groups.<br...

Antihypertensive Effects of Huotan Jiedu Tongluo in H-Type Hypertensive Rats

<ol>
	<li>Noone, C., Dwyer, C. P., Murphy, J., Newell, J., Molloy, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparative+effectiveness+of+physical+activity+interventions+and+antihypertensive+pharmacological+interventions+in+reducing+blood+pressure+in+people+with+hypertension:+Protocol+for+a+systematic+review+and+network+meta-analysis.">Comparative effectiveness of physical activity interventions and antihypertensive pharmacological interventions in reducing blood pressure in people with hypertension: Protocol for a systematic review and network meta-analysis.</a> Syst Rev. 7 (1), 128 (2018).</li><li>Huang, K., Zhang, Z., Huang, S., Jia, Y., Zhang, M., Yun, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+association+between+retinal+vessel+abnormalities+and+h-type+hypertension.">The association between retinal vessel abnormalities and h-type hypertension.</a> BMC Neurol. 21 (1), 6 (2021).</li><li>Tan, Y., Nie, F., Wu, G., Guo, F., Wang, Y., Wang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+h-type+hypertension+on+intraplaque+neovascularization+assessed+by+contrast-enhanced+ultrasound.">Impact of h-type hypertension on intraplaque neovascularization assessed by contrast-enhanced ultrasound.</a> J Atheroscler Thromb. 29 (4), 492-501 (2022).</li><li>Towfighi, A., Markovic, D., Ovbiagele, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pronounced+association+of+elevated+serum+homocysteine+with+stroke+in+subgroups+of+individuals:+A+nationwide+study.">Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: A nationwide study.</a> J Neurol Sci. 298 (1-2), 153-157 (2010).</li><li>Zhong, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+homocysteine+and+blood+pressure+related+to+poor+outcome+of+acute+ischemia+stroke+in+Chinese+population.">High homocysteine and blood pressure related to poor outcome of acute ischemia stroke in Chinese population.</a> Plos One. 9 (9), e107498 (2014).</li><li>Hao, P., Jiang, F., Cheng, J., Ma, L., Zhang, Y., Zhao, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traditional+Chinese+medicine+for+cardiovascular+disease:+Evidence+and+potential+mechanisms.">Traditional Chinese medicine for cardiovascular disease: Evidence and potential mechanisms.</a> J Am Coll Cardiol. 69 (24), 2952-2966 (2017).</li><li>Tian, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Huotan+Jiedu+Tongluo+decoction+inhibits+balloon-injury-induced+carotid+artery+intimal+hyperplasia+in+the+rat+through+the+perk-eif2&#945;-atf4+pathway+and+autophagy+mediation.">Huotan Jiedu Tongluo decoction inhibits balloon-injury-induced carotid artery intimal hyperplasia in the rat through the perk-eif2&#945;-atf4 pathway and autophagy mediation.</a> Evid Based Complement Alternat Med. 2021, 5536237 (2021).</li><li>Simko, F., Pechanova, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potential+roles+of+melatonin+and+chronotherapy+among+the+new+trends+in+hypertension+treatment.">Potential roles of melatonin and chronotherapy among the new trends in hypertension treatment.</a> J Pineal Res. 47 (2), 127-133 (2009).</li><li>Li, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=H-type+hypertension+is+a+risk+factor+for+cerebral+small-vessel+disease.">H-type hypertension is a risk factor for cerebral small-vessel disease.</a> BioMed Res Int. 2020, 6498903 (2020).</li><li>Rodrigo, R., Passalacqua, W., Araya, J., Orellana, M., Rivera, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Homocysteine+and+essential+hypertension.">Homocysteine and essential hypertension.</a> J Clin Pharmacol. 43 (12), 1299-1306 (2003).</li><li>Lehmann, M., Gottfries, C. G., Regland, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+cognitive+impairment+in+the+elderly:+Homocysteine+is+an+early+marker.">Identification of cognitive impairment in the elderly: Homocysteine is an early marker.</a> Dement Geriatr Cogn. 10 (1), 12-20 (1999).</li><li>dos Santos, E. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+that+folic+acid+deficiency+is+a+major+determinant+of+hyperhomocysteinemia+in+Parkinson's+disease.">Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson's disease.</a> Metab Brain Dis. 24 (2), 257-269 (2009).</li><li>Zhao, W., Gao, F., Lv, L., Chen, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+interaction+of+hypertension+and+homocysteine+increases+the+risk+of+mortality+among+middle-aged+and+older+population+in+the+United+States.">The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States.</a> J Hypertens. 40 (2), 254-263 (2022).</li><li>Woo, K. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperhomocyst(e)inemia+is+a+risk+factor+for+arterial+endothelial+dysfunction+in+humans.">Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.</a> Circulation. 96 (8), 2542-2544 (1997).</li><li>Lu, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+intervention+of+enalapril+maleate+and+folic+acid+tablet+on+the+expressions+of+the+grp78+and+chop+and+vascular+remodeling+in+the+vascular+smooth+muscle+cells+of+h-hypertensive+rats+with+homocysteine.">The intervention of enalapril maleate and folic acid tablet on the expressions of the grp78 and chop and vascular remodeling in the vascular smooth muscle cells of h-hypertensive rats with homocysteine.</a> Eur Rev Med Pharmaco. 22 (7), 2160-2168 (2018).</li><li>L&#243;pez-Garc&#237;a, P., Moreira, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+forces+for+the+origin+of+the+eukaryotic+nucleus.">Selective forces for the origin of the eukaryotic nucleus.</a> BioEssays. 28 (5), 525-533 (2006).</li><li>Minamino, T., Komuro, I., Kitakaze, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endoplasmic+reticulum+stress+as+a+therapeutic+target+in+cardiovascular+disease.">Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease.</a> Circ Res. 107 (9), 1071-1082 (2010).</li><li>Chen, X., Cubillos-Ruiz, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endoplasmic+reticulum+stress+signals+in+the+tumour+and+its+microenvironment.">Endoplasmic reticulum stress signals in the tumour and its microenvironment.</a> Nat Rev Cancer. 21 (2), 71-88 (2021).</li><li>Ji, C., Kaplowitz, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperhomocysteinemia,+endoplasmic+reticulum+stress,+and+alcoholic+liver+injury.">Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury.</a> World J Gastroentero. 10 (12), 1699-1708 (2004).</li><li>Zhang, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Homocysteine+induces+programmed+cell+death+in+human+vascular+endothelial+cells+through+activation+of+the+unfolded+protein+response.">Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response.</a> J Biol Chem. 276 (38), 35867-35874 (2001).</li><li>Cunard, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endoplasmic+reticulum+stress,+a+driver+or+an+innocent+bystander+in+endothelial+dysfunction+associated+with+hypertension.">Endoplasmic reticulum stress, a driver or an innocent bystander in endothelial dysfunction associated with hypertension.</a> Cur Hypertens Rep. 19 (8), 64 (2017).</li><li>Casas, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=GRP78+at+the+centre+of+the+stage+in+cancer+and+neuroprotection.">GRP78 at the centre of the stage in cancer and neuroprotection.</a> Front Neurosci. 11, 177 (2017).</li><li>Urano, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coupling+of+stress+in+the+ER+to+activation+of+JNK+protein+kinases+by+transmembrane+protein+kinase+ire1.">Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase ire1.</a> Science. 287 (5453), 664-666 (2000).</li><li>Borghi, A., Verstrepen, L., Beyaert, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TRAF2+multitasking+in+tnf+receptor-induced+signaling+to+nf-&#954;b,+map+kinases+and+cell+death.">TRAF2 multitasking in tnf receptor-induced signaling to nf-&#954;b, map kinases and cell death.</a> Biochem Pharmacol. 116, 1-10 (2016).</li><li>Wen, X. -. 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Hypertension is one of the most common cardiovascular disorders that affects one-third of the adult population and increases the risk of stroke, coronary heart disease, and heart and renal failure8. H-type hypertension is a special type of hypertension that refers to the co-occurrence of primary hypertension and increased homocysteine levels and has attracted broad attention over the years9. In recent years, the use of oral EM combined with antihypertensive drugs has shown ...

Hypertension, a major risk factor for heart attack, stroke, and renal failure, has become a significant public health challenge that affects 1 billion people worldwide1. Homocysteine (Hcy), a thiol group-containing amino acid, is a vital metabolic intermediary of methionine metabolism. Hypertension with elevated plasma Hcy levels is defined as H-type hypertension, which could be a significant risk factor for the occurrence and recurrence of cardiocerebrovascular diseases such as stroke2,3. Recent studies have reported that the co-residency of H-type hypertension could aggravate the side effects of cardiovascular and cerebrovascular diseases4. Notably, 75% of patients in China with H-type hypertension have primary hypertension, which seriously affects the quality of life5. At present, the treatment of H-type hypertension mainly includes Western medicine. However, it may cause certain adverse effects and poor compliance and can no longer meet the needs for the comprehensive management of H-type hypertension.
Traditional Chinese medicine (TCM) is a unique resource with a history of more than 2,000 years in China. Due to the unmet need for hypertension control in Western medicine, clinicians have begun to consider the potential role of TCM in the prevention and treatment of H-type hypertension6. Huotan Jiedu Tongluo Decoction (HTJDTLD) is a traditional Chinese medicine formula formulated by Professor Yue Deng, drawing from his extensive clinical expertise7. Over the course of more than 20 years of clinical application, HTJDTLD has demonstrated remarkable effectiveness in the treatment of cardiovascular and cerebrovascular diseases1. However, whether HTJDTLD has therapeutic effects in H-type hypertension has not been reported. Therefore, we aimed to explore the antihypertensive effects and specific mechanisms of HTJDTLD in rats with H-type hypertension and identify potential therapeutic drugs for the treatment of H-type hypertension.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>1st Strand cDNA Synthesis SuperMix for qPCR</td>
			<td>Yeasen,China</td>
			<td>11149ES</td>
			<td>cDNA synthesis kit&#160;</td>
		</tr>
		<tr>
			<td>Anti-beta-actin antibody</td>
			<td>Bioss, China</td>
			<td>bs-0061R</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-caspase-3 antibody</td>
			<td>Bioss, China</td>
			<td>bs-0081R</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-GPR78 antibody</td>
			<td>Abcam, USA</td>
			<td>ab108513</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-JNK antibody</td>
			<td>Abcam, USA</td>
			<td>ab76572</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-p-JNK antibody</td>
			<td>Bioss, China</td>
			<td>bsm-52462R</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-rabbit IgG antibody</td>
			<td>Bioss, China</td>
			<td>bs-0295G-HRP</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-TRAF2 antibody</td>
			<td>Bioss, China</td>
			<td>bs-22372R</td>
			<td></td>
		</tr>
		<tr>
			<td>Bio-Rad CFX96 Touch system&#160;</td>
			<td>Bio-Rad</td>
			<td>CFX96</td>
			<td>real-time PCR detection system&#160;</td>
		</tr>
		<tr>
			<td>ECL Western Blot Substrates</td>
			<td>Merck, MA, USA</td>
			<td>WBULP-10ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Enalapril maleate folic acid tablets</td>
			<td>Yangzijiang Pharmaceutical Company, China</td>
			<td>20040991</td>
			<td></td>
		</tr>
		<tr>
			<td>FastStart SYBR Green Master</td>
			<td>Sigma</td>
			<td>FSSGMMRO</td>
			<td></td>
		</tr>
		<tr>
			<td>Fructus Trichosanthis</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Hirudo</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>intelligent noninvasive sphygmomanometer&#160;</td>
			<td>Beijing Softron Biotechnology company</td>
			<td>BP-2010A</td>
			<td></td>
		</tr>
		<tr>
			<td>Lonicerae Japonicae Flos</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Methionine</td>
			<td>Sigma, USA</td>
			<td>M9500</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix Angelicae Sinensis</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix et Rhizoma Glycyrrhizae</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix et Rhizoma Nardostachyos</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix et Rhizoma Rhodiolae Crenulatae</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix et Rhizoma Salviae Miltiorrhizae</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Radix Scrophulariae</td>
			<td>The First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, China</td>
			<td>No catalog number</td>
			<td></td>
		</tr>
		<tr>
			<td>Rat Hcy ELISA Kits</td>
			<td>Shanghai Meimian Industrial Company, China</td>
			<td>MM-0293R2</td>
			<td></td>
		</tr>
		<tr>
			<td>RIPA buffer</td>
			<td>Shanghai Beyotime Biotechnology company</td>
			<td>P0013B</td>
			<td></td>
		</tr>
	</tbody>
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the antihypertensive effects and mechanisms of huotan jiedu tongluo decoction in rats with h-type hypertension

H-type hypertension, which is a specific form of hypertension characterized by elevated plasma homocysteine (Hcy) levels, has become a major public health challenge worldwide. This study investigated the hypotensive effects and underlying mechanisms of Huotan Jiedu Tongluo decoction (HTJDTLD), a highly effective traditional Chinese medicine formula commonly used to treat vascular stenosis. Methionine was used to induce H-type hypertension in rats, and HTJDTLD was administered intragastrically. Then, the systolic and diastolic blood pressures of the caudal artery of rats were measured by noninvasive rat caudal manometry. Histological assessment of the aorta was performed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure Hcy levels, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were used to determine the mRNA and protein levels of Glucose regulatory protein 78 (GRP78), Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), c-Jun N-terminal&#160;kinases (JNK), and caspase-3. The results showed that HTJDTLD significantly lowered blood pressure, alleviated histopathological lesions, and decreased Hcy levels after methionine treatment. Moreover, HTJDTLD significantly inhibited the gene and protein expression of GRP78, JNK, TRAF2, and caspase 3, which are involved mainly in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. Overall, the results indicated that HTJDTLD had effective antihypertensive effects in rats with H-type hypertension and revealed the antihypertensive mechanisms associated with inhibition of ER stress-induced apoptosis pathway activation.

Author Spotlight: Exploring Huotan Jiedu Tongluo Decoction as an Antihypertensive Drug

The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension

H-type hypertension has become a significant public health challenge of human. It mainly relies on Western medicine treatment, which can have sad effects. Our research explores the anti-hypertensive effects and mechanisms of Huotan Jiedu Tongluo decoction, a traditional Chinese medicine formula, in rats with H-type hypertension.Our study indicated that Huotan Jiedu Tongluo decoction had anti-hypertensive effects in rats with H-type hypertension. The underlying mechanism may involve inhibiting ER stress activation-induced apoptosis which provide an effective treatment option for patients. We will explode the potential biomarkers for early diagnosis and prognosis and develop novel therapeutic drugs for H-type hypertension in the future.

As shown in Table 4 and Table 5, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly greater in the MET group than those in the CON group from 1 to 4 weeks. After HTJDTLD treatment, the SBP and DBP of the rats were significantly lower than those in the MET group. Notably, the combined utilization of HTJDTLD and EM had a stronger antihypertensive effect than HTJDTLD treatment alone.
According to HE staining and Masson&#39;s t...

Read this Scientific Article Protocol about The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension at JoVE.com

Here, we present a protocol to induce H-type hypertension and evaluate the antihypertensive effects of Huotan Jiedu Tongluo decoction (HTJDTLD) administered intragastrically. In rats with H-type hypertension, HTJDTLD had effective antihypertensive effects, possibly associated with inhibition of endoplasmic reticulum (ER) stress-induced apoptosis pathway activation.

H-type hypertension, which is a specific form of hypertension characterized by elevated plasma homocysteine (Hcy) levels, has become a major public health ...

the-antihypertensive-effects-mechanisms-huotan-jiedu-tongluo