Chemical Profile Determination and Quantitative Analysis of Components in Oryeong-san Using UHPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS.

In this study, a method to both qualitatively and quantitively analyze the components of Oryeong-san (ORS), which is composed of five herbal medicines (Alisma orientale Juzepzuk, Polyporus umbellatus Fries, Atractylodes japonica Koidzumi, Poria cocos Wolf, and Cinnamomum cassia Presl) and is prescribed in traditional Oriental medicine practices, was established for the first time. First, ORS components were profiled using ultra-high-performance liquid chromatography/quadrupole Orbitrap mass spectrometry, and 19 compounds were clearly identified via comparison against reference standard compounds. Subsequently, a quantitative method based on ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry was established to simultaneously measure the identified compounds. Nineteen compounds were accurately quantified using the multiple-reaction-monitoring mode and used to analyze the sample; we confirmed that coumarin was the most abundant compound. The method was validated, achieving good linearity (R2 ≤ 0.9991), recovery (RSD, 0.11-3.15%), and precision (RSD, 0.35-9.44%). The results suggest that this method offers a strategy for accurately and effectively determining the components of ORS, and it can be used for quality assessment and management.

Treatment of nausea and vomiting associated with cerebellar infarction using the traditional herbal medicines banhabaekchulcheonma-tang and oryeong-san: Two case reports (CARE-complaint).

RATIONALE: Metoclopramide is commonly used to treat nausea and vomiting. However, long-term administration of metoclopramide is associated with various adverse effects, and its therapeutic effects are short-lasting. Hence, traditional East Asian medicine has received increasing attention as a short-term strategy for treating these symptoms. PATIENT CONCERNS: The present report discusses the cases of a 71-year-old man and an 80-year-old woman diagnosed with cerebellar infarction. Both patients reported nausea and vomiting, which appeared during hospitalization following cerebellar infarction. DIAGNOSES: One patient was diagnosed with a left cerebellar infarction and hemorrhagic transformation, while the other was diagnosed with a bilateral cerebellar infarction. INTERVENTIONS: Both patients took Banhabaekchulcheonma-tang (BT) and Oryeong-san (OS) extracts. OUTCOMES: The patient in Case 1 experienced a rapid decrease in nausea from day 5 of BT and OS administration, and metoclopramide was discontinued on day 7. The patient in Case 2 experienced a clear decrease in the number of vomiting episodes from day 6 of BT and OS administration and did not take metoclopramide thereafter. LESSONS: Other than drugs used to mitigate symptoms, there are no suitable treatments available for nausea and vomiting caused by cerebellar infarction. In the present cases, nausea and vomiting remained unresolved even after 3 weeks of treatment with conventional therapies; however, these symptoms significantly improved after administration of the traditional East Asian herbal medicines BT and OS, and there were no recurrences. These cases demonstrate that traditional herbal medicine can reduce the side effects associated with long-term administration of metoclopramide and help patients resume their daily lifestyle. In addition, BT and OS treatment can facilitate administration of other drugs, highlighting its potential to aid in the treatment of stroke. Further research including relevant clinical trials is required to obtain more conclusive evidence.

A systems pharmacology approach to investigate the mechanism of Oryeong-san formula for the treatment of hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Oryeong-san (ORS) is a traditional formula that has long been used for the treatment of dysfunctions of body fluids and electrolyte homeostasis in Korea, China and Japan. Recent reports have shown that ORS may suppress hypertension by controlling the renin-angiotensin-aldosterone system (RAAS) in the kidney, but its action mechanism has not been well defined. AIM OF THE STUDY: The aim of this study was to decipher the ORS mechanisms in the treatment of hypertension using a systems pharmacology approach. MATERIALS AND METHODS: The compounds of ORS were obtained from the TM-MC (database of medicinal materials and chemical compounds in Northeast Asian traditional medicine), and the drug-likeness (DL) and oral bioavailability (OB) of the compounds were evaluated. The potential targets of the compounds were identified using various pharmacology databases. To analyze the mechanisms of the ORS for hypertension, a Compound-Target-Disease (C-T-D) network was established with respect to the genes related to hypertension. RESULTS: A screening evaluation of the DL and OB of the ORS compounds identified a list of 232 active compounds. The pharmacological activity of the targets was investigated by exploring the interaction network between the compounds and the targets. Analysis of the interactions between the compounds and the hypertension-related targets revealed that 14 ORS compounds regulate the RAAS and vasoconstrictors in the kidney. CONCLUSIONS: This study used the systems pharmacology approach to decipher the mechanisms of action of ORS for the treatment of hypertension. When hypertension drugs and ORS are used in combination for treatment, possible side effects should be considered because most hypertension drugs are related to the RAAS. The results of this study may provide clues to not only analyze the pharmacological activity of ORS for the treatment of hypertension but other diseases as well.

Safety assessment of Oryeong-san, a traditional herbal formula: Study of subacute toxicity and influence of cytochrome P450s and UDP-glucuronosyltransferases.

Oryeong-san is a traditional herbal formula that is used for the treatment of common genitourinary diseases in Korea and other Asian countries. However, little is known about its safety and influence on drug metabolism. In the present study, we investigated the subacute toxicity of an Oryeong-san water extract (OSWE) in rats and its effects on activities of drug-metabolizing enzymes. Subacute toxicity was modeled in animals exposed to treatment with the extract at multiple doses. Rats were given OSWE by oral gavage at 0, 1000, 2000 and 5000 mg/kg/day for 4 weeks. We checked general observations and investigated any changes of body/organ weight, food consumption, hematology, serum biochemistry, and urinalysis in vivo; and the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferase (UGT) isozymes in vitro. We found that OSWE caused no significant toxicological changes at the doses tested. Therefore, the no observed adverse effect level of OSWE was more than 5000 mg/kg/day for male and female rats. OSWE inhibited the activities of CYP2C19 (IC50: 737.69 µg/mL) and CYP2E1 (IC50: 177.77 µg/mL). These results indicate that OSWE may be safe with no drug-related toxicity for up to 4 weeks and provide useful information concerning its potential to interact with conventional drugs or other herbal medicines.