참당귀

1. Nutrients. 2024 Apr 11;16(8):1137. doi: 10.3390/nu16081137. A 12-Week, Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial for the Evaluation of the Efficacy and Safety of Lactiplantibacillus plantarum SKO-001 in Reducing Body Fat. Shin SM(1), Park JS(2

BACKGROUND/AIM: Colorectal cancer (CRC) continues to pose substantial clinical challenges owing to the limited response and emergent resistance to standard chemotherapeutic regimens, including FOLFOX. The present investigation explored the antitumor efficacy of JI-CJ002, a standardized herbal formula consisting of Angelica gigas, Aconitum carmichaeli, and Zingiber officinale (2:1:3 ratio), and its combined effects with FOLFOX in in vitro settings. MATERIALS AND METHODS: Cytotoxic activities were assessed in HT29 and HCT116 human colorectal cancer cell lines by conducting MTT assays, Annexin V/7-AAD staining, and western blotting. Network pharmacology techniques were employed to identify common targets among JI-CJ002, FOLFOX, and CRC-associated gene profiles. RESULTS: JI-CJ002 exhibited broad-spectrum cytotoxicity that was both time- and dose-dependent in HT29 and HCT116 cell lines. Network analysis identified 89 common targets predominantly involved in DNA repair, apoptosis, and chemoresistance pathways. The combination treatment led to a significant, synergistic reduction in cell viability and elevated apoptotic markers, including Annexin V/7-AAD positivity and cleaved PARP. Mechanistically, co-treatment inhibited ATM, ATR, p-CHK1, p-CHK2, p-Cdc2, and p-p53, while sustaining γ-H2AX accumulation, signifying persistent DNA damage and inadequate activation of cell cycle arrest checkpoints. Immunofluorescence revealed a further increase in γ-H2AX nuclear foci. CONCLUSION: JI-CJ002 augments the therapeutic effect of FOLFOX by suppressing DNA damage response and inducing aberrant cell cycle progression, thereby supporting its development as a chemo-sensitizing agent for colorectal cancer therapy.

BACKGROUND: Cancer remains one of the leading causes of death worldwide, underscoring the need for novel therapies. SH003, an herbal mixture composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, is a traditional Korean medicine formulation with potential to enhance chemotherapy efficacy and reduce toxicity. This study aimed to assess the safety and determine maximum tolerated dose of SH003 in combination with docetaxel in patients with advanced solid tumors, specifically lung and breast cancer. METHODS: This Phase I, multi-center, open-label, dose-escalation study enrolled patients with advanced lung or breast cancer. Participants received SH003 orally at doses of 2400, 3600, or 4800 mg daily, alongside intravenous docetaxel (75 mg/m²) every 21 days. A 3 + 3 dose-escalation design was employed to determine the maximum tolerated dose. Safety assessments and adverse event monitoring were conducted at each treatment cycle. RESULTS: Twelve participants were enrolled. SH003 was well tolerated up to 4800 mg/day, with no dose-limiting toxicities attributed to SH003. The most common adverse events were neutropenia, primarily associated with docetaxel, and mild dermatologic reactions such as eczema, rash acneiform, and pruritus. Preliminary evidence of disease stabilization was observed in several participants. CONCLUSION: The combination of SH003 and docetaxel demonstrated a favorable safety profile, with 4800 mg/day identified as maximum tolerated dose for SH003. These findings support further investigation in Phase II trials to assess therapeutic efficacy.Trial Registration: Clinical Research Information Service (https://cris.nih.go.kr) KCT0004770.

BACKGROUND: The immune system is essential for defending the body against pathogens and maintaining homeostasis. Recent global public health challenges have increased interest in natural products that enhance immune function. SH003, a compound derived from Astragalus membranaceus, Angelica gigas Radix, and Trichosanthis Radix, has shown potential as an immunomodulatory agent. This study aims to evaluate the efficacy and safety of SH003 in improving immune function in individuals with a mildly weakened immune systems. METHODS: This randomized, double-blind, placebo-controlled trial will be conducted over 8 weeks with 120 participants aged 19 to 75 years who have experienced two or more upper respiratory infections in the past year. Participants will be randomly assigned to receive either SH003 or a placebo. The primary outcome is the change in natural killer cell activity. Secondary outcomes include cytokines levels (IL-2, IL-12, IFN-γ, TNF-α), inflammation markers (CRP, ESR), and stress and respiratory symptoms. Safety outcomes will be monitored through vital signs and laboratory tests. DISCUSSION: This study represents the first clinical trial to evaluate the immune-enhancing effects of SH003 in a general population with mild immune system impairment. The results could offer valuable insights into the potential of SH003 as a novel immune support intervention. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0009424, May 10, 2024, https://cris.nih.go.kr ). Retrospectively registered. © 2025. The Author(s).

Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, Cmax 1x), decursinol angelate (DA, Cmax ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, Cmax ~ 1000x). Here we update in vivo medicinal activities of AGN and/or its pyranocoumarins and furanocoumarin nodakenin in cancer, pain, memory loss, cerebral ischemia reperfusion stroke, metabolic syndrome and vascular endothelial dysfunctions, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, osteoporosis and osteoarthritis. Given their polypharmacology nature, the pertinent mechanisms of action are likely misrepresented by many cell culture studies that did not consider the drug metabolism knowledge. We report here Rho-associated protein kinases (ROCK1/2) as novel targets for DA and DOH. Combining with published inhibitory activity of DOH on acetylcholinesterase, agonist activity of DOH and antagonist/degrader activity of DA/D on androgen and estrogen receptors, D/DA promoting activity for glutamic acid decarboxylase (GAD)- gamma-aminobutyric acid (GABA) inhibitory axis and inhibition of glutamate dehydrogenase (GDH), monoamine oxidase-A (MAO-A) and transient receptor potential vanilloid 1 (TRPV1), we postulate their contributions to neuro-cognitive, metabolic, oncologic, vascular and other beneficial bioactivities of AGN extracts. A clinical trial is being planned for an AGN extract to manage side effects of androgen deprivation therapy in prostate cancer patients. © 2025. The Author(s).

Cancer ranks as the first leading cause of death globally. Despite the various types of cancer treatments, negative aspects of the treatments, such as side effects and drug resistance, have been a continuous dilemma for patients. Thus, natural compounds and herbal medicines have earned profound interest as chemopreventive agents for reducing burden for patients. SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, showed the potential to act as an anticancer agent in previous research studies. A narrative review was conducted to present the significant highlights of the total 15 SH003 studies from the past nine years. SH003 has shown positive results in both in vivo and vitro studies against various types of cancer cells; furthermore, the first clinical trial was performed to identify the maximum tolerated dose among solid cancer patients. So far, the potential of SH003 as a chemotherapeutic agent has been well-documented in research studies; continuous work on SH003's efficacy and safety is required to facilitate better cancer patient care but is part of the knowledge needed to understand whether SH003 has the potential to become a pharmaceutical.

INTRODUCTION: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer. METHODS: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel. DISCUSSION: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04360317.

Background: Cancer is a major health problem worldwide and the leading cause of death in many countries. Preclinical studies have shown the therapeutic anticancer effects of SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. The present study investigated the maximum tolerated dose of SH003 in patients with solid cancers. Methods: This open-label, dose-escalation trial used the traditional 3 + 3 dose-escalation design. Patients with solid cancers were recruited and administered 1 to 4 tablets of SH003 thrice daily for 3 weeks according to the dose level. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Dose-limiting toxicities (DLTs) were defined as Grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. Results: The present study enrolled 11 patients. A total of 31 adverse events occurred. According to the CTCAE, all the observed adverse events were grade 2 or less and no adverse events of grade 3 or more corresponding to DLT occurred. Conclusion: The study results indicated that the maximum tolerated dose of SH003 was 4800 mg/day. A Phase 2 study is required to determine the efficacy of SH003 in patients with cancer at a dose of 4800 mg/day or less.

Angelica gigas Nakai, Korean dang-gui, has long been widely used in traditional treatment methods. There have been a number of studies of the health effects of A. gigas and related compounds, but studies addressing effects on blood triglycerides (TG) are lacking. To investigate the effects of A. gigas Nakai extract (AGNE) on TG in Korean subjects, we carried out a 12-week, randomized, double-blind, placebo-controlled clinical trial. Subjects who met the inclusion criterion (130 mg/dL ≤ fasting blood TG ≤ 200 mg/dL) were recruited for this study. One hundred subjects were assigned to the AGNE group (n = 50) or the placebo group (n = 50), who were given 1 g/day of AGNE (as a gigas Nakai extract 200 mg/d) in capsules and the control group for 12 weeks. Outcomes were efficacy TG, lipid profiles, atherogenic index, and safety parameters were assessed initially for a baseline measurement and after 12 weeks. After 12 weeks of supplementation, TG and very low-density lipoprotein cholesterol (VLDL-C) concentration and TG/HDL-C ratio in the AGNE group were significantly reduced compared to the placebo group (p < 05). No significant changes in any safety parameter were observed. These results suggest that the ingestion of AGNE may improve TG and be useful to manage or prevent hypertriglyceridemia.

INTRODUCTION: Cancer is a major health problem worldwide and the leading cause of death in many countries. The number of patients with cancer and socioeconomic costs of cancer continues to increase. SH003 is a novel herbal medicine consisting of Astragalus membranaceus, Angelica gigas and Trichosanthes Kirilowii Maximowicz. Preclinical studies have shown that SH003 has therapeutic anticancer effects. The aim of this study is to determine the maximum tolerated dose of SH003 in patients with solid cancers. METHODS AND ANALYSIS: This study is an open-label, dose-escalation trial evaluating the safety and tolerability of SH003. The traditional 3+3 dose-escalation design will be implemented. Patients with solid cancers will be recruited. According to dose level, the patients will receive one to four tablets of SH003, three times a day for 3 weeks. Toxicity will be evaluated using common terminology criteria for adverse events (CTCAE). Dose-limiting toxicities are defined as grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose will be determined by the highest dose at which no more than one of six patients experiences dose-limiting toxicity. ETHICS AND DISSEMINATION: This study has been approved by the institutional review board of the Ajou University Hospital (reference AJIRB-MED-CT1-16-311). The results of this study will be disseminated through a scientific journal and a conference. TRIAL REGISTRATION NUMBER: NCT03081819; Pre-results. © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

ETHNOPHARMACOLOGICAL RELEVANCE: Infertility is a global public health issue related to gynecological diseases and psychological disorders such as stress, depression, and fatigue. Prescriptions of various herbs in traditional East Asian medicine (TEAM) have recently gained attention among patients as a complementary alternative therapy for female infertility. However, studies on systemic analysis of the use of herbal medicines according to TEAM patterns or the therapeutic effects of herbal medicines on female infertility are limited. AIM OF THE STUDY: We aimed to systematically investigate the single herb and TEAM patterns that are commonly used for treating female infertility using network analysis. Additionally, we performed a meta-analysis to assess the effect of herbal medicine on the pregnancy rate in women with infertility. MATERIALS AND METHODS: PubMed, EMBASE, Korean Studies Information Service System, Science ON, Research Information Sharing Service, and Oriental Medicine Advanced Searching Integrated System were searched for randomized controlled trials (RCTs) reporting the pregnancy rate of herbal medicine for infertility until July 2021. Following identifying the top three herbs used in treating female infertility, a network analysis was performed to reveal the TEAM pattern relationships between each herb. A meta-analysis was performed to evaluate the therapeutic effect of herbal medicine on pregnancy rate. Moreover, the methodological quality of RCTs was analyzed using Consolidated Standards of Reporting Trials (CONSORT) extension guidelines and the Risk of bias (RoB) tool. RESULTS: Eighteen RCTs with 2,662 participants were included. Cuscuta chinensis Lam. (Tusizi) is the most commonly used herb for treating female infertility, followed by Angelica gigas Nakai (Danggui) and Cyperus rotundus L. (Xiangfuzi). These herbs were mainly used to treat patients with kidney deficiency or kidney deficiency combined with blood stasis or Phlegm-dampness on the TEAM pattern. The meta-analysis revealed that the effect of herbal medicine led to a significant increase in pregnancy rates compared to the placebo treatment. Adverse events in the included studies were g