• San-Huang-Xie-Xin-Tang (SHXXT)
• breast cancer
• mortality
• population
• risk

Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.

• active components
• mechanism
• pulmonary arterial hypertension
• reverse pharmacology
• traditional herbal medicines

• Animals
• Antihypertensive Agents/isolation & purification
• Antihypertensive Agents/pharmacology
• Berberine/isolation & purification
• Berberine/pharmacology
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cells, Cultured
• Coptis chinensis
• Cytochrome P-450 CYP1B1/metabolism
• Databases, Genetic
• Disease Models, Animal
• Drugs, Chinese Herbal/isolation & purification
• Drugs, Chinese Herbal/pharmacology
• Hypertrophy, Right Ventricular/metabolism
• Hypertrophy, Right Ventricular/pathology
• Hypertrophy, Right Ventricular/physiopathology
• Hypertrophy, Right Ventricular/prevention & control
• Mitogen-Activated Protein Kinase 1/metabolism
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/metabolism
• Muscle, Smooth, Vascular/pathology
• Muscle, Smooth, Vascular/physiopathology
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• Myocytes, Smooth Muscle/pathology
• NADPH Oxidase 4/metabolism
• Network Pharmacology
• Pulmonary Arterial Hypertension/metabolism
• Pulmonary Arterial Hypertension/pathology
• Pulmonary Arterial Hypertension/physiopathology
• Pulmonary Arterial Hypertension/prevention & control
• Pulmonary Artery/drug effects
• Pulmonary Artery/metabolism
• Pulmonary Artery/pathology
• Pulmonary Artery/physiopathology
• Quercetin/isolation & purification
• Quercetin/pharmacology
• Rats, Sprague-Dawley
• Signal Transduction
• Vascular Remodeling/drug effects
• Ventricular Function, Right/drug effects
• Rats

• Ministry of Science and Technology, Taiwan

• Dioscin
• GRB2/ERK/PI3K-AKT signal
• Molecular mechanism
• Pulmonary arterial smooth muscle cells
• Vascular remodeling

• Animals
• Apoptosis/drug effects
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cells, Cultured
• Diosgenin/analogs & derivatives
• Diosgenin/pharmacology
• Disease Models, Animal
• Extracellular Signal-Regulated MAP Kinases/metabolism
• GRB2 Adaptor Protein/genetics
• GRB2 Adaptor Protein/metabolism
• Male
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/enzymology
• Muscle, Smooth, Vascular/pathology
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/enzymology
• Myocytes, Smooth Muscle/pathology
• Phosphatidylinositol 3-Kinase/metabolism
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Pulmonary Arterial Hypertension/drug therapy
• Pulmonary Arterial Hypertension/enzymology
• Pulmonary Arterial Hypertension/pathology
• Pulmonary Artery/drug effects
• Pulmonary Artery/enzymology
• Pulmonary Artery/pathology
• Rats, Sprague-Dawley
• Signal Transduction
• Vascular Remodeling/drug effects
• Rats

It has been reported that Sanoshashinto (SanHuangXieXinTang, 三黃瀉心湯), which is composed of Rhei Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, exhibits vasorelaxant effects in vitro and lowers blood pressure of patients. Based on this discovery, in this study, a mixture containing those three materials and combinations of them were extracted with methanol, and the extracts were fractionated into different parts. Effects of all extracts and fractions on high concentration of potassium chloride (High K⁺)- or noradrenaline (NA)-induced contractions of isolated rat aortic rings or helical strips were examined. Qualitative and quantitative HPLC analyses of the extracts and the fractions revealed that the contents of baicalin and berberine in Sanoshashinto methanol extract (SHXXTM) were higher than those of the other constituents. All pharmacological and HPLC data were analyzed by principal component analysis (PCA) software and the results indicated that baicalin, berberine, palmatine, baicalein, and wogonoside contributed significantly to the pharmacological activity. Furthermore, spontaneously hypertensive rats (SHRs) that were orally given SHXXTM or a baicalin–berberine combination showed significantly reduced increase in the rate of systolic blood pressure (SBP) compared to the control group. These findings suggested that Sanoshashinto has significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine, which were the principal constituents of Scutellariae Radix and Coptidis Rhizoma, were the main antihypertensive constituents in Sanoshashinto. It was speculated that baicalin and berberine produced vasorelaxant effects by activating the NO/cGMP pathway and that the BK_Ca channel and the DAG/PKC/CPI-17 pathway were also involved.

• Antihypertensive
• Baicalin
• Berberine
• Principal component analysis
• Sanoshashinto
• Vasorelaxant effect

• Anti-migration
• Anti-proliferative
• Neointima hyperplasia
• Scutellaria strigillosa Hemsley
• VSMCs

• Animals
• Becaplermin/administration & dosage
• Carotid Intima-Media Thickness
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Chromatography, High Pressure Liquid
• Dose-Response Relationship, Drug
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular/cytology
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/metabolism
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• Plant Extracts/administration & dosage
• Plant Extracts/pharmacology
• Rats
• Scutellaria/chemistry
• Tandem Mass Spectrometry

• AHPND
• Disease resistance
• Enrofloxacin
• Immunomodulation
• Litopenaeus vannamei
• San-Huang-San
• Vibrio parahaemolyticus

• Animals
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/therapeutic use
• Drugs, Chinese Herbal/administration & dosage
• Drugs, Chinese Herbal/therapeutic use
• Enrofloxacin/administration & dosage
• Enrofloxacin/therapeutic use
• Immunity, Innate/drug effects
• Necrosis/prevention & control
• Penaeidae/drug effects
• Penaeidae/immunology
• Vibrio parahaemolyticus/drug effects

• Prunus yedoensis
• hyperlipidemia
• hypertension
• safety
• spontaneous hypertensive rats
• toxicity
• traditional medicine

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology.

• Coptidis Rhizoma
• antipyretic
• cognitive functions
• heat stress
• neuroinflammation

• Animals
• Antipyretics/pharmacology
• Behavior, Animal/drug effects
• Body Temperature Regulation/drug effects
• Brain/drug effects
• Brain/metabolism
• Brain/pathology
• Brain/physiopathology
• Brain Diseases/etiology
• Brain Diseases/pathology
• Brain Diseases/physiopathology
• Brain Diseases/prevention & control
• Cell Death/drug effects
• Cognition/drug effects
• Cognitive Dysfunction/etiology
• Cognitive Dysfunction/physiopathology
• Cognitive Dysfunction/prevention & control
• Cognitive Dysfunction/psychology
• Coptis chinensis
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Fever/complications
• Fever/drug therapy
• Fever/physiopathology
• Heat Stress Disorders/complications
• Heat Stress Disorders/drug therapy
• Heat Stress Disorders/physiopathology
• Hydrocortisone/blood
• Male
• Maze Learning/drug effects
• Memory/drug effects
• Mice, Inbred ICR
• Motor Activity/drug effects
• Neuroprotective Agents/pharmacology
• Phytotherapy
• Plants, Medicinal
• Signal Transduction/drug effects

Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A_2A receptor (A_2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo.

We established a hypoxia-induced pulmonary hypertension (HPH) mouse model by subjecting wild-type (WT) and A_2AR knockout (A_2AR^−/−) animals to chronic hypoxia, and we examined the effects of a 4-week treatment with baicalin or the A_2AR agonist CGS21680 in these animals. Invasive hemodynamic parameters, the right ventricular hypertrophy index, pulmonary congestion, the pulmonary arterial remodeling index, blood gas parameters, A_2AR expression, and the expression of SDF-1/CXCR4/PI3K/protein kinase B (PKB; AKT) signaling components were measured.

Compared with WT mice, A_2AR^−/− mice exhibited increased right ventricular systolic pressure (RVSP), right ventricle-to-left ventricle plus septum [RV/(LV + S)] ratio, RV weight-to-body weight (RV/BW) ratio, and lung wet weight-to-body weight (Lung/BW) ratio in the absence of an altered mean carotid arterial pressure (mCAP). These changes were accompanied by increases in pulmonary artery wall area and thickness and reductions in arterial oxygen pressure (P_aO₂) and hydrogen ion concentration (pH). In the HPH model, A_2AR^−/− mice displayed increased CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression compared with WT mice. Treating WT and A_2AR^−/− HPH mice with baicalin or CGS21680 attenuated the hypoxia-induced increases in RVSP, RV/(LV + S) and Lung/BW, as well as pulmonary arterial remodeling. Additionally, baicalin or CGS21680 alone could reverse the hypoxia-induced increases in CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression. Moreover, baicalin improved the hypoxemia induced by 4 weeks of hypoxia. Finally, we found that A_2AR levels in WT lung tissue were enhanced by hypoxia and that baicalin up-regulated A_2AR expression in WT hypoxic mice.

Baicalin exerts protective effects against clinical HPH, which are partly mediated through enhanced A_2AR activity and down-regulated SDF-1/CXCR4-induced PI3K/AKT signaling. Therefore, the A_2AR may be a promising target for baicalin in treating HPH.

• Adenosine A2A
• Baicalin
• CXCR4
• Pulmonary arterial hypertension
• Receptor
• SDF-1

Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects. In this study, we focus on the effects of BSYSC on promoting nerve repair and the underlying mechanisms in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

The EAE mouse model was induced by injecting subcutaneously with myelin oligodendrocyte glycoprotein (MOG) _35–55 supplemented with pertussis toxin. BSYSC was orally administrated at dose of 3.0 g/kg once a day for 40 days. The levels of protein gene product (PGP) 9.5, p-Tau, growth associated protein (GAP) -43, KI67 and Nestin in the brain or spinal cord on 20 and 40 day post-induction (dpi) were detected via immunofluorescence and Western blot analysis. Furthermore, NogoA/NgR and RhoA/ROCK signaling molecules were studied by qRT-PCR and Western blot analysis.

Twenty or 40 days of treatment with BSYSC increased markedly PGP9.5 and GAP-43 levels, reduced p-Tau in the brain or spinal cord of mice with EAE. In addition, BSYSC elevated significantly the expression of KI67 and Nestin in the spinal cord 40 dpi. Further study showed that the activation of NogoA/NgR and RhoA/ROCK were suppressed by the presence of BSYSC.

BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.

• Bu Shen Yi sui capsule
• Experimental autoimmune encephalomyelitis
• Gap-43
• KI67
• Multiple sclerosis
• Nestin
• NogoA/NgR
• P-tau
• PGP9.5
• RhoA/ROCK

San-Huang-Xie-Xin-Tang (SHXXT), one of the most important traditional Chinese medicinal formulas, is comprised by three herbal medicines, the rhizome of Rheum officinale [or Rheum tanguticum (Polygonaceae) (Dahuang in Chinese)], the root of Scutellaria baicalensis (Labiatae) (Huangqin in Chinese), and the rhizome of Coptis chinensis (Ranunculaceae) (Huanglian in Chinese) in the ratios of 2:1:1 or 1:1:1. This study is aimed to quantitate and qualify of SHXXT, by a rapid, convenient, and effective HPLC-PDA approach associated with LC-MS technique. Of which method, nine chosen major bioactive components in SHXXT, including aloe-emodin (Ale), baicalin (Ba), berberine (Be), coptisine (Co), palmatine (Pa), resveratroloside (Res), rhein (Rh), sennoside A (Se-A), and wogonin (Wo), were evaluated within 30 min. The nine chemical markers were monitored in a high sensitivity with a low detection limit of 0.01−0.55 μg/mL and the correlation coefficient of the regression curve revealed a good linearity with R² > 0.99. Moreover, the extraction solution system and the HPLC elution conditions were also optimized in the present study. This present developed protocol was then successfully applied to quantify nine chemical markers of 10 SHXXT products from eight Taiwanese TCM pharmaceutical companies. In quantitative results, Res was found as the major compound in SHXXT-1~5 and 8 with significantly higher amounts than those in other products, indicating the products SHXXT-1~5 and 8 may use R. tanguticum as the raw material, which possessed a higher concentration of the bioactive composition Res, instead of R. officinale. Simultaneously, Ale, Rh, and Wo were < 2% in these 10 products. Different chemical profiles of commercial products indicated that, probably, each product with the same named formula might be regarded as a sole medicine and need to be investigated individually. Importantly, it is never too much to emphasize the importance of quality control in TCM development.

• Coptis chinensis
• HPLC
• Rheum officinale
• Rheum tanguticum
• San-Huang-Xie-Xin-Tang (SHXXT)
• Scutellaria baicalensis
• quality control
• quantification

Chunghyul-dan (CHD) is a herbal complex containing 80% ethanol extract and is composed of Scutellariae Radix, Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, and Rhei Rhizoma. We have published several experimental and clinical research articles on CHD. It has shown antilipidemic, antihypertensive, antiatherosclerotic, and inhibitory effects on ischemic stroke recurrence with clinical safety in the previous studies. The antilipidemic effect of CHD results from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and pancreatic lipase-inhibitory activity. The antihypertensive effect likely results from the inhibitory effect on endogenous catecholamine(s) release and harmonization of all components showing the antihypertensive effects. Furthermore, anti-inflammatory and antioxidant effects on endothelial cells are implicated to dictate the antiatherosclerotic effects of CHD. It also showed neuroprotective effects on cerebrovascular and parkinsonian models. These effects of CHD could be helpful for the prevention of the recurrence of ischemic stroke. Therefore, we suggest that CHD could be a promising medication for treating and preventing cerebrovascular and cardiovascular diseases. However, to validate and better understand these findings, well-designed clinical studies are required.

The present study was designed to evaluate the antihypertensive effect of GaMiSamHwangSaSimTang (HVC1), a 30% ethanol extract of a mixture comprising Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma, on spontaneous hypertensive rats (SHRs). The systolic blood pressure (SBP) was measured every 4 or 7 days using the noninvasive tail cuff system. The vasorelaxant effects on isolated aortic rings were evaluated. Aortic rings were contracted using phenylephrine (PE) or KCl, and the changes in tension were recorded via isometric transducers connected to a data acquisition system. In this study, oral administration of HVC1 decreased the SBP of SHRs over the experimental period. HVC1 induced concentration-dependent relaxation in the aortic rings that had been precontracted using PE or KCl. The vasorelaxant effects of HVC1 on endothelium-intact aortic rings were inhibited by pretreatment with Nω-Nitro-l-arginine methyl ester (L-NAME) or methylene blue. HVC1 inhibited the contraction induced by extracellular Ca²⁺ in endothelium-denuded rat aortic rings that had been precontracted using PE or KCl. In conclusion, HVC1 reduced the SBP of SHR and relaxed isolated SHR aortic rings by upregulating NO formation and the NO-cGMP pathway and blocking the entry of extracellular Ca²⁺ via receptor-operative Ca²⁺ channel and voltage-dependent Ca²⁺ channel.

• neuronal nitric oxide synthase inhibition
• oxidative stress
• rhoa/rock
• smooth muscle tone
• superoxide anions

• Gastrointestinal disorders
• Gastrointestinal tract
• Intestinal transit rate
• Motility
• San-Huang-Xie-Xin-Tang

• Acetic Acid
• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Gastrointestinal Agents/pharmacology
• Gastrointestinal Diseases/chemically induced
• Gastrointestinal Diseases/drug therapy
• Gastrointestinal Diseases/physiopathology
• Gastrointestinal Motility/drug effects
• Male
• Mice, Inbred ICR
• Streptozocin
• Time Factors

• 5-hydroxytryptamine
• Gastrointestinal disorders
• Interstitial cells of Cajal
• San-Huang-Xie-Xin-Tang
• Traditional Chinese medicine

• Animals
• Calcium/metabolism
• Chloride Channels/drug effects
• Chloride Channels/metabolism
• Drugs, Chinese Herbal/pharmacology
• Female
• Interstitial Cells of Cajal/drug effects
• Interstitial Cells of Cajal/metabolism
• Intestine, Small/cytology
• Intestine, Small/drug effects
• Intestine, Small/metabolism
• Male
• Membrane Potentials/drug effects
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases/metabolism
• Patch-Clamp Techniques
• Receptors, Serotonin, 5-HT3/metabolism
• Receptors, Serotonin, 5-HT4/metabolism

• Animals
• Anthraquinones/blood
• Anthraquinones/pharmacokinetics
• Berberine/pharmacokinetics
• Caco-2 Cells
• Dogs
• Drug Interactions
• Flavonoids/blood
• Flavonoids/pharmacokinetics
• Glucuronides/metabolism
• Humans
• Intestinal Mucosa/metabolism
• Male
• Rats
• Rats, Wistar

San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1–methyl–4–phenylpyridinium (MPP⁺)/1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) models of Parkinson's disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP⁺ in vitro and MPTP in vivo. In MPP⁺-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP⁺-induced gp91^phox activation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP⁺-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection.

• Animals
• Calcium/metabolism
• Cell Proliferation/drug effects
• Cells, Cultured
• Endothelin-1/physiology
• Female
• Flavanones/isolation & purification
• Flavanones/pharmacology
• Flow Cytometry
• Muscle, Smooth, Vascular/cytology
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/metabolism
• Protein Kinase C-alpha/antagonists & inhibitors
• Pulmonary Artery/cytology
• Pulmonary Artery/drug effects
• Pulmonary Artery/metabolism
• Rats
• Rats, Sprague-Dawley
• Scutellaria baicalensis/chemistry
• TRPC Cation Channels/antagonists & inhibitors
• TRPC Cation Channels/metabolism

• Animals
• Antihypertensive Agents/pharmacology
• Blood Pressure/drug effects
• Cells, Cultured
• Cucurbitaceae/chemistry
• In Vitro Techniques
• Male
• Nitric Oxide/biosynthesis
• Nitric Oxide/physiology
• Rats
• Rats, Wistar
• Swine

• cyclooxygenase‐2
• hepatitis c virus
• nuclear factor‐κb
• san‐huang‐xie‐xin‐tang
• synergistic

• cholecystokinin
• coptis chinensis rhizomes
• irritable bowel syndrome
• neonatal maternal separation
• ranunculaceae
• serotonin

• Abdominal Pain/drug therapy
• Abdominal Pain/etiology
• Analgesics/pharmacology
• Analgesics/therapeutic use
• Animals
• Cholecystokinin/metabolism
• Colon/drug effects
• Colon/metabolism
• Colon/pathology
• Coptis
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Electromyography/methods
• Hyperalgesia/drug therapy
• Hyperalgesia/etiology
• Irritable Bowel Syndrome/complications
• Irritable Bowel Syndrome/drug therapy
• Male
• Maternal Deprivation
• Muscle, Smooth/drug effects
• Muscle, Smooth/pathology
• Pain Threshold/drug effects
• Phytotherapy
• Rats
• Rats, Sprague-Dawley
• Rhizome
• Serotonin/metabolism
• Stress, Psychological

• U19 AT003266 NCCIH NIH HHS
• U19 AT003266-01 NCCIH NIH HHS
• 1-U19-AT003266 NCCIH NIH HHS

• Aorta/cytology
• Atherosclerosis/drug therapy
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cells, Cultured
• Cyclooxygenase 2/genetics
• Cyclooxygenase 2/metabolism
• Drugs, Chinese Herbal/pharmacology
• Ethnopharmacology
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Humans
• Inflammation Mediators/metabolism
• Medicine, Chinese Traditional
• Myocytes, Smooth Muscle/cytology
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• Phytotherapy
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Reactive Oxygen Species/metabolism
• Taiwan