Blood-Pressure-Lowering and Endothelium-Dependent Vasorelaxant Effects of Nutgall Tree in Rats.

Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Rhus chinensis Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K+ channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.

Hypotensive and Vasorelaxant Effects of Sanguisorbae Radix Ethanol Extract in Spontaneously Hypertensive and Sprague Dawley Rats.

Hypertension requires proper management because of the increased risk of cardiovascular disease and death. For this purpose, functional foods containing tannins have been considered an effective treatment. Sanguisorbae radix (SR) also contains various tannins; however, there have been no studies on its vasorelaxant or antihypertensive effects. In this study, the vasorelaxant effect of the ethanol extract of SR (SRE) was investigated in the thoracic aorta of Sprague Dawley rats. SRE (1, 3, 10, 30, and 100 µg/mL) showed this effect in a dose-dependent manner, and its mechanisms were related to the NO/cGMP pathway and voltage-gated K+ channels. Concentrations of 300 and 1000 µg/mL blocked the influx of extracellular Ca2+ and inhibited vasoconstriction. Moreover, 100 µg/mL of SRE showed a relaxing effect on blood vessels constricted by angiotensin II. The hypotensive effect of SRE was investigated in spontaneously hypertensive rats (SHR) using the tail-cuff method. Blood pressure significantly decreased 4 and 8 h after 1000 mg/kg of SRE administration. Considering these hypotensive effects and the vasorelaxant mechanisms of SRE, our findings suggests that SRE can be used as a functional food to prevent and treat hypertension. Further studies are needed for identifying the active components and determining the optimal dosage.

Chemical Constituents from Roots of Sophora davidii (Franch.) Skeels and Their Glucose Transporter 4 Translocation Activities.

Sophora davidii (Franch.) Skeels is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of S. davidii, a chemical investigation was thus performed. In this research, two new stilbene oligomers, Davidiol E-F (1-2), one new 4-aryl-substituted isoflavan Davidinin A (3), and one new 2-arylbenzofuran dimer, Shandougenine C (4), as well as six known compounds (5-10) were obtained from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. The absolute configuration of 1-3 was assigned by comparing its experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-10 promoted glucose transporter 4 (GLUT-4) translocations by the range of 1.28-2.60 folds, respectively. Compound 9 showed the most potent glucose transporter 4 translocations with 1.60 fold enhancement. The result attained in this study indicated that the separation and characterization of these compounds plays an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.

Anti-esophageal Cancer Effect of Corilagin Extracted from Phmllanthi Fructus via the Mitochondrial and Endoplasmic Reticulum Stress Pathways.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose) is a tannin isolated from the traditional ethnopharmacological plant Phmllanthi Fructus, which is widely used in not only traditional Chinese medicine but also tropical and subtropical medicine to ameliorate various diseases. AIM OF THE STUDY: This study was designed to isolate the potential anti-esophageal cancer (EC) component corilagin from Phmllanthi Fructus and explain its anti-EC mechanism. MATERIALS AND METHODS: Corilagin was isolated from Phmllanthi Fructus by extraction and chromatographic procedures, and its anti-esophageal cancer effect was evaluated by in vitro and in vivo experiments. In vitro experiments included MTT analysis, flow cytometry, and the Transwell assay and were used to observe corilagin-mediated inhibition of EC cell growth. Western blotting was used to analyze the apoptotic pathway of EC cells. In vivo experiments used tumor-bearing nude mice to evaluate the antitumor effect of corilagin, and its potential mechanism was explored by Western blotting. RESULTS: Corilagin showed significant anti-EC activity in vitro and in vivo. Corilagin was significantly cytotoxic to EC cells and induced apoptosis in EC cells. Corilagin induced G0/G1 phase arrest by altering key G0/G1 cell cycle regulatory markers and significantly reducing the migration of EC cells and the number of cells in a time- and dose-dependent manner. Additionally, corilagin inhibited the growth of transplanted tumors in nude mice without significant toxicity. Regarding the anticancer mechanism of corilagin, the results showed that corilagin inhibited esophageal cancer progression by activating mitochondrial and endoplasmic reticulum stress signaling pathways. CONCLUSIONS: Corilagin shows significant anti-EC activity in vitro and in vivo. The mechanism of the anti-EC activity of corilagin may be due to activating mitochondrial and endoplasmic reticulum stress signaling pathways.

Vasorelaxant Effect of Prunus mume (Siebold) Siebold & Zucc. Branch through the Endothelium-Dependent Pathway.

Korean plum (Prunus mume (Siebold) Siebold & Zucc.) has long been used as a health food or herbal medicine in Asia. Previous studies have shown that several plants of the genus Prunus have vasodilatory and antihypertensive effects; we hypothesized that P. mume branches may have a vasorelaxant effect. In this study, we evaluated the effects and action mechanism of 70% ethanol extract of P. mume branch (PMB) on isolated rat aortic rings. Inhibitors such as NG-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, methylene blue, indomethacin, atropine, tetraethylammonium chloride, glibenclamide, 4-aminopyridine and BaCl2 were used to investigate the mechanism of vasodilation responsible for the vascular relaxation. PMB (2-30 µg/mL) induced vasorelaxation in the presence of vascular endothelium, and all inhibitors used in this study affected the degree of relaxation. These results suggest that the vasorelaxant effect of PMB is endothelium-dependent and affects the nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin pathway, muscarinic receptor pathway, and potassium channels. Our study explains that PMB may be another approach to hypertension treatment to reduce the burden of cardiovascular disease.

Endothelium-Dependent Vasorelaxant Effect of Prunus Persica Branch on Isolated Rat Thoracic Aorta.

Peach (Prunus persica (L.) Batsch) is a popular fruit consumed by people worldwide, owing to its pleasant flavor and high mineral nutrient content. A few plants from the genus Prunus, such as Prunus yedoensis, Prunus cerasus, and Prunus serotina have shown vasorelaxant and vasodilatory effects, to date, no study has investigated the vasorelaxation effects of the P. persica branch extract (PPE). The vasorelaxant effect of PPE was endothelium-dependent, and it was related to the NO-sGC-cGMP, vascular prostacyclin, and muscarinic receptor transduction pathway. K+ channels, such as the BKCa, KV, and KATP channels, were partially associated with PPE-induced vasorelaxation. PPE was effective in relaxing serotonin (5-HT)- or angiotensin II-induced contraction; furthermore, PPE attenuated Ca2+-induced vasoconstriction by IP3 receptors in the SR membrane, but its vasorelaxant effect was not associated with the influx of extracellular Ca2+ via receptor-operative Ca2+ channels or voltage-dependent Ca2+ channels. Recognizing the rising use of functional foods for hypertension treatment, our findings imply that PPE may be a natural antihypertensive agent.

Thirteen-Week Oral Toxicity Study of HVC1 in Rats.

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.

Vasorelaxant and Hypotensive Effects of Cheonwangbosimdan in SD and SHR Rats.

Historically, traditional herbal medicines (THMs) have been the conventional treatment strategy in the Korean medical system for treating many diseases. However, THMs have rarely been used to treat hypertension, and moreover few studies have investigated the interaction of blood pressure with the coadministration of synthetic antihypertensives. We aimed to evaluate the vasorelaxant and hypotensive effects of the traditional herbal prescription Cheonwangbosimdan (CWBSD; "Tianwangbuxindan" in Chinese) and the combination of CWBSD with amlodipine. CWBSD was extracted with distilled water at 100°C for 2 h. To investigate vasorelaxant activities, CWBSD with amlodipine (10 µg/ml) was added cumulatively (10-1,000 µg/ml) to isolated rat aortic rings precontracted using phenylephrine or potassium chloride in organ chambers. To investigate hypotensive effects, CWBSD (2,476 mg/kg) was orally administered with or without amlodipine (5 mg/kg) to spontaneously hypertensive rats (SHRs). CWBSD increased the relaxation of rat aortic rings induced by amlodipine (P < 0.01). In vivo, CWBSD coadministration with amlodipine also significantly decreased the blood pressure of SHRs compared to the amlodipine-treated group. These results suggested that CWBSD could be a useful herbal prescription to treat hypertension and we recommend establishing guidelines for the use of herbal medicines in conjunction with antihypertensive drugs, including amlodipine.

Experimental research of hypotensive and hypolipidemic effects with Modified Sanhuang Xiexin Decoction ().

OBJECTIVE: To investigate the hypotensive and hypolipidemic effects of Modified Sanhuang Xiexin Decoction (, HVC1), a herbal prescription for the vascular diseases in Chinese medicine and evaluate the acute and subchronic oral toxicities. METHODS: Fifty-six spontaneous hypertensive rats (SHRs) were used to investigate the hypotensive and hypolipidemic effect of HVC1. Rats in the normal group (n=8) were fed with normal diet. The rats in the other groups (n=48) were fed with high fat and cholesterol diet for inducing hyperlipidemia models. Forty-eight rats were randomly divided into 6 groups [model, positive control (amlodipine, simvastain), 50, 250, and 1,000 mg/(kg•d) HVC1 groups] with 8 animals in each group. Normal and model groups were treated with distilled water [1 mL/(kg•d)], the positive control group was treated with amlodipine [5 mg/(kg•d)] or simvastatin [10 mg/(kg•d)], and the HVC1 groups were treated with HVC1 [50, 250, or 1,000 mg/(kg•d)] for 8 weeks, respectively. Blood pressure (BP) of the rats was measured using a non-invasive tail cuff system. On the last day of the experiment, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were measured. To investigate the safety of HVC1, acute and subchronic toxicity studies were conducted on Sprague-Dawley rats. In toxicity studies, the body weight, food and water consumption of rats were measured and clinical signs observation, ophthalmologic examinations, urinalysis, hematological analysis, and serum biochemical analysis were performed. RESULTS: A dose of 50 and 250 mg/(kg•d) HVC1 lowered systolic and diastolic BP (P<0.05). HVC1 at 1,000 mg/(kg•d) decreased TC, LDL-C and TG levels, respectively (P<0.01 or P<0.05) and 250 mg/(kg•d) HVC1 decreased TG levels on hyperlipidemic SHRs (P<0.05). In the acute toxicity study, oral administration of HVC1 did not show any toxicity effect, and the median lethal dose value of HVC1 was greater than 5,000 mg/kg. In the subchronic toxicity study, oral administration of HVC1 for 4 weeks also did not show any toxicity effect, and the no-observedadverse-effect-level of HVC1 was established as 2,000 mg/(kg•d). CONCLUSION: These results could be used as preclinical data for clinical trials that develop HVC1 as a herbal medicine for treating or preventing hypertension and hyperlipidemia.

Vasorelaxant effects of Angelica decursiva root on isolated rat aortic rings.

BACKGROUND: Hypertension is one of the most important risk factors for cardiovascular disease (CVD) and a worldwide problem. Despite increases in the development of synthetic drugs for hypertension treatment, the rate of untreated and uncontrolled hypertension remains high. These drugs are effective, but can also cause side effects. Approximately 80% of the world population uses herbal medicines because of their low toxicity and better acceptability by the human body. Therefore, we attempted to identify natural medications for treating hypertension. The 70% ethanol extract of Angelica decursiva root (ADE) shows strong vasorelaxant potential, but no studies have investigated the mechanisms underlying the vasorelaxation effect of A. decursiva. METHODS: Dried root of A. decursiva was identified by DNA sequencing and was extracted once with 1 L 70% ethanol (EtOH) for 3 h in a reflux apparatus at 70 °C. ADE was evaluated for its vasorelaxant effects in rat thoracic aortas. Various inhibitors of ADE-induced vasorelaxation were used. RESULTS: ADE showed vasorelaxant effects on the intact and denuded endothelium of aortic rings pre-contracted with phenylephrine and KCl in Krebs-Henseleit solution. Tetraethylammonium and 4-aminopyridine did not alter ADE-induced vasorelaxation. However, the vasorelaxant effect of ADE was partially inhibited by pre-treatment with glibenclamide an ATP-sensitive K+ channel blocker. Furthermore, ADE concentration-dependently inhibited Ca2+ supplementation-induced vasoconstriction of aortic rings that had been pretreated with phenylephrine or KCl in Ca2+-free Krebs-Henseleit solution. CONCLUSIONS: These results suggest that ADE-induced vasorelaxation occurred in an endothelium-independent manner. The vasorelaxant effects of ADE were correlated with blockade of the KATP channel and inhibition of Ca2+ influx via receptor-operative Ca2+ channels or voltage-dependent Ca2+ channels.

Wound Healing Effects of Prunus yedoensis Matsumura Bark in Scalded Rats.

Pruni Cortex has been used to treat asthma, measles, cough, urticaria, pruritus, and dermatitis in traditional Korean medicine. The objective of this study was to investigate the effects of Prunus yedoensis Matsumura bark methanol extract (PYE) on scald-induced dorsal skin wounds in rats. Scalds were produced in Sprague-Dawley rats with 100°C water and treated with 5% and 20% PYE (using Vaseline as a base), silver sulfadiazine (SSD), and Vaseline once a day for 21 days, beginning 24 hours after scald by treatment group allocation. The PYE-treated groups showed accelerated healing from 12 days after scald, demonstrated by rapid eschar exfoliation compared to the control and SSD groups. PYE-treated groups showed higher wound contraction rates and better tissue regeneration in comparison with the control group. Serum analysis showed that transforming growth factor beta 1 and vascular endothelial growth factor levels remained high or gradually increased up to day 14 in both PYE groups and then showed a sharp decline by day 21, implying successful completion of the inflammatory phase and initiation of tissue regeneration. These findings suggested that PYE is effective in promoting scald wound healing in the inflammation and tissue proliferation stages.

HVC1 ameliorates hyperlipidemia and inflammation in LDLR-/- mice.

BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR-/-) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6 groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or 250 mg/kg, p.o.). RESULTS: HVC1 regulated the levels of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the transcription level of the peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X receptor (LXR), and inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Furthermore, HVC1 activated 5' adenosine monophosphate-activated protein kinase (AMPK). CONCLUSION: Our results suggest that HVC1 might be effective in preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes involved in cholesterol and lipid metabolism, and inflammatory responses.

Hypolipidemic effects of HVC1 in a high cholesterol diet­induced rat model of hyperlipidemia.

HVC1, a novel formation containing four herbs, was developed and its hypolipidemic effects in rats with high cholesterol diet (HCD)­induced hyperlipidemia were investigated. The rats were given a HCD for 8 weeks. The HVC1­treated groups were orally administered HVC1 at doses of 10, 50 or 250 mg/kg, respectively, and the simvastatin group was treated at a dose of 10 mg/kg. The normal diet and HCD control groups were administered with physiological saline. Oral administration of HVC1 (10, 50 or 250 mg/kg) significantly reduced the body weight of rats with hyperlipidemia and regulated the total cholesterol, low­density lipoprotein cholesterol and high­density lipoprotein cholesterol levels in the serum. In addition, tissue analysis revealed that lipid accumulation in the liver and aorta was reduced by HVC1 administration. Furthermore, HVC1 significantly reduced the mRNA expression of peroxisome proliferator­activated receptor­Î³, 3­hydroxy­3­methylglutaryl­CoA reductase and low­density lipoprotein receptor, as well as the protein level of 5' adenosine monophosphate­activated protein kinase in the liver. The results clearly demonstrate that HVC1 has a potent hypolipidemic effect, and suggest that HVC1 should be evaluated as a potential treatment for hyperlipidemia.

Effect of Acer tegmentosum bark on atopic dermatitis-like skin lesions in NC/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a chronic and relapsing inflammatory condition characterized by pruritic and eczematous skin lesions that requires safe and effective pharmacological therapy. The bark of Acer tegmentosum Maxim trees has been used in Korean folk and traditional medicine to treat abscesses, surgical bleeding, liver diseases, and AD. AIM OF STUDY: To investigate the therapeutic effect of A. tegmentosum, on a mouse model of Dermatophagoides farinae (Df)-induced AD. METHODS: Development of AD-like skin lesions was induced by repetitive skin contact with barrier-disrupted backs of NC/Nga mice with Df body ointment, and the effects of A. tegmentosum were evaluated on the basis of histopathological skin assessment results, ear swelling, and cytokine production in the dorsal skin. The component of A. tegmentosum, salidroside, inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. RESULTS: Topical application of A. tegmentosum for 1 week after Df body ointment challenge significantly reduced ear swelling and improved dorsal skin lesions. Suppression of dermatitis by combined therapy was accompanied by a decrease in the skin level of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, plasma levels of thymus and activation-regulated chemokine, and IgE. Induction of thymic stromal lymphopoietin, which leads to a systemic Th2 response, was also reduced in in vivo and in vitro by A. tegmentosum and salidroside. CONCLUSIONS: Our findings suggest that A. tegmentosum treatment has a significant therapeutic effect on Df-induced AD-like skin lesions on NC/Nga mice through inhibition of thymic stromal lymphopoietin and IgE via a mechanism that may inhibit Th2-mediated immune responses. These results suggest that A. tegmentosum and salidroside may be useful tools for the treatment of AD.

Antihypertensive Effect of the GaMiSamHwangSaSimTang in Spontaneous Hypertensive Rats.

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 Ca(2+) 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 Ca(2+) via receptor-operative Ca(2+) channel and voltage-dependent Ca(2+) channel.

Investigation of the mechanisms of Angelica dahurica root extract-induced vasorelaxation in isolated rat aortic rings.

BACKGROUND: The root of Angelica dahurica Bentham et Hooker (Umbelliferae) has been used as a traditional medicine for colds, headache, dizziness, toothache, supraorbital pain, nasal congestion, acne, ulcer, carbuncle, and rheumatism in China, Japan, and Korea. Interestingly, it has been used in the treatment of vascular diseases including hypertension. The aim of this study was to provide pharmacological evidence for the anti-hypertensive effect of A. dahurica by investigating the mechanism underlying its vasorelaxant effect. METHODS: The vasorelaxant effects of a 70% methanol extract of the A. dahurica root (ADE) on rat thoracic aorta and its underlying mechanisms were assessed. Isolated rat aortic rings were suspended in organ chambers containing 10 ml Krebs-Henseleit (K-H) solution and placed between 2 tungsten stirrups and connected to an isometric force transducer. Changes in tension were recorded via isometric transducers connected to a data acquisition system. RESULTS: ADE causes concentration-dependent relaxation in both endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine (PE; 1 µM) or potassium (KCl; 60 mM) in K-H solution. And pre-treatment with ADE (1 mg/ml) inhibited calcium-induced vasocontraction of aortic rings induced by PE or KCl. However, ADE pre-treatment did not affect the contraction induced by PE or caffeine in Ca(2+)-free K-H solution. CONCLUSIONS: These results suggested that the ADE has vasorelaxant effect and the vasorelaxant activity is mediated by endothelium-independent pathway that includes the blockade of extracellular calcium influx through the receptor-operated Ca(2+) channel and voltage-dependent calcium channel pathways.

Effect of Ampelopsis Radix on wound healing in scalded rats.

BACKGROUND: Ampelopsis Radix has been used as a traditional Korean medicine for the treatment of burns and scalds. However, there has been no scientific research to date on the wound healing properties of Ampelopsis Radix for scald burns. This study aimed to evaluate the healing effect of Ampelopsis japonica root tuber ethanol extract (AJE) on induced cutaneous scald injury in Sprague Dawley (SD) rats. METHODS: Hot water scalds were induced in SD rats, who were then divided into the following 5 groups; 1) control group without treatment, 2) positive control group with 1% Silver sulfadiazine (SSD), 3) Vaseline group, and groups 4) and 5) that used Vaseline containing 5% and 20% AJE, respectively. The ointment was applied topically to the experimental rats, once daily for 21 days, starting at 24 h post induction of the scald injury. Gross examination, measurement of wound size, and histopathological examination were performed. And quantitative measurement of cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor beta 1 (TGF-ß1), and vascular endothelial growth factor (VEGF) were performed by enzyme-linked immunosorbent assay. RESULTS: Clinical evaluation showed that the AJE and Vaseline groups, rapidly desquamated scab on day 12 post-scalding; in particular, the 20% AJE group achieved the greatest extent of skin recovery. Sizes of scald wound were significantly lower on days 12, 15, 18, and 21 in the AJE treated groups compared to the control groups. Histopathological evaluation showed a well-organized epithelial layer, angiogenesis, tissue granulation and collagen formation with the exception of inflammatory cells in the AJE-treated groups compared to the control groups on day 14, indicating that tissue regeneration had occurred. AJE treatment decreased TNF-α and increased IL-10 levels on days 2 and 14, indicating the anti-inflammatory action of AJE. The AJE groups also showed a decrease in TGF-ß1 levels on day 7 and VEGF on day 14 in the serum of scald inflicted SD rat model. CONCLUSIONS: These results suggest that AJE possesses scald wound healing activity via accelerating the scald wound repair during the inflammation and proliferative phases of the healing process.

Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta.

Ligusticum jeholense has been used as the traditional medicine 'Go-Bon' (Chinese name, Gao-ben) in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L. jeholense. We tested the methanol (MeOH) extract of L. jeholense root and rhizoma for vasorelaxant effects; while using an isolated organ-chamber technique, L. jeholense extract (LJE) induced relaxation in the rat aortic rings by stimulating vascular endothelial and smooth muscle cells. LJE showed concentration-dependent relaxant effects on endothelium-intact and endothelium-denuded aortic rings pre-contracted with both phenylephrine (PE) and potassium chloride (KCl) in Krebs-Henseleit (KH) buffer. The vasorelaxant effect of LJE was partly attenuated by pre-treatment with glibenclamide or 4-aminopyridine (4-AP) as K+ channel blockers. Moreover, LJE showed concentration-dependent inhibition of vasoconstriction by Ca2+ supplementation in the aortic rings that were pre-contracted with PE or KCl in Ca2+-free KH buffer. In addition, a combination of LJE and nifedipine, pre-incubated further, decreased PE-induced contractions. The results suggested that LJE-induced vasorelaxation were related to blocking K+ channels and inhibiting entry of extracellular Ca2+ via receptor-operative Ca2+ channels (ROCCs) or voltage-dependent Ca2+ channels (VDCCs).

Effects of Eucommia ulmoides extract on longitudinal bone growth rate in adolescent female rats.

Eucommia ulmoides is one of the popular tonic herbs for the treatment of low back pain and bone fracture and is used in Korean medicine to reinforce muscles and bones. This study was performed to investigate the effects of E. ulmoides extract on longitudinal bone growth rate, growth plate height, and the expressions of bone morphogenetic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) in adolescent female rats. In two groups, we administered a twice-daily dosage of E. ulmoides extract (at 30 and 100 mg/kg, respectively) per os over 4 days, and in a control group, we administered vehicle only under the same conditions. Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling. Chondrocyte proliferation in the growth plate was observed using cresyl violet dye. In addition, we analyzed the expressions of BMP-2 and IGF-1 using immunohistochemistry. Eucommia ulmoides extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats. In the immunohistochemical study, E. ulmoides markedly increased BMP-2 and IGF-1 expressions in the proliferative and hypertrophic zones. In conclusion, E. ulmoides increased longitudinal bone growth rate by promoting chondrogenesis in the growth plate and the levels of BMP-2 and IGF-1. Eucommia ulmoides could be helpful for increasing bone growth in children who have growth retardation.

Prunus yedoensis bark inhibits lipopolysaccharide-induced inflammatory cytokine synthesis by IκBα degradation and MAPK activation in macrophages.

The bark of Prunus yedoensis is used in antitussive medicines and in oral herbal formulations for inflammatory skin disorders. In the present study, we explored whether P. yedoensis bark extract (PYE) and its solvent partitioned fractions could modulate lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 in vivo and in vitro. In addition, we examined the effect of PYE extract and its fractions on LPS-induced NF-κB and mitogen-activated protein kinase (MAPK) signaling in mouse peritoneal macrophages. Oral treatment of PYE decreased serum levels of TNF-α and IL-6 in LPS injected mice. PYE inhibited LPS-induced TNF-α and IL-6 in macrophages at the transcriptional level and also suppressed LPS-induced IκBα degradation and MAPK activation in vitro. Among the fractions, the chloroform fraction, which contains genistein, naringenin, sakuranetin, prunetin, and amygdalin, showed inhibitory effects at much lower concentrations than the water and ethyl acetate fractions. Taken together, our results indicate that PYE was able to inhibit LPS-induced expression of TNF-α and IL-6, the latter of which was more prominent. The effects of PYE on inflammatory cytokine synthesis may involve modulation of NF-κB and MAPK activation.