Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

A Review of Herbal Resources Inducing Anti-Liver Metastasis Effects in Gastrointestinal Tumors via Modulation of Tumor Microenvironments in Animal Models.

Liver metastases remain a major obstacle for the management of all types of tumors arising from digestive organs, and the tumor microenvironment has been regarded as an important factor in metastasis. To discover herbal candidates inhibiting the liver metastasis of tumors originating from the digestive system via the modulation of the tumor microenvironment and liver environment, we searched three representative public databases and conducted a systematic review. A total of 21 studies that employed experimental models for pancreatic (9), colon (8), and stomach cancers (4) were selected. The herbal agents included single-herb extracts (5), single compounds (12), and multiherbal decoctions (4). Curcuma longa Linn was most frequently studied for its anti-colon-liver metastatic effects, and its possible mechanisms involved the modulation of tumor microenvironment components such as vascular endothelial cells and immunity in both tumor tissues and circulating cells. The list of herbal agents and their mechanisms produced in this study is helpful for the development of anti-liver metastasis drugs in the future.

Adjuvant effect of herbal medicine on transarterial chemoembolization in patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Objectives: Primary hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, especially in Asian countries. As a practical treatment option, transarterial chemoembolization (TACE) has been well applied; however, its limited efficacy remains challenging. This study analyzed the adjuvant effects of herbal medicine on TACE to determine whether it improves clinical outcomes in patients with HCC. Methods: A systematic review and meta-analysis was performed to compare the adjuvant effects of herbal medicine on TACE versus TACE therapy alone. We searched the literature from eight databases since January 2011. Results: Twenty-five studies involving 2,623 participants were selected. The adjuvant therapy of herbal medicine on TACE improved the overall survival at 0.5 years (OR = 1.70; 95% CI 1.21-2.38), 1 year (OR = 2.01; 95% CI 1.65-2.46), 2 years (OR = 1.83; 95% CI 1.20-2.80), and 3 years (OR = 1.90; 95% CI 1.25-2.91). The combination therapy also increased the tumor response rate (OR = 1.84; 95% CI 1.40-2.42). Conclusions: Despite the unsatisfactory quality of the included studies, the adjuvant therapy of herbal medicine on TACE may provide survival benefits to patients with HCC. Systematic reviews registration: http://www.crd.york.ac.uk/PROSPERO, identifier (376691).

Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase.

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

A survey of herbal medicines as tumor microenvironment-modulating agents.

The tumor microenvironment (TME) is extremely complex, involving extensive interactions among stromal cells, immune cells, and signaling molecules. Therefore, an approach targeting the TME has emerged as a promising therapeutic strategy. Herbal medicines consist of multiple active compounds, which have multi-target effects. Therefore, they have been regarded as potential anticancer agents; multiple studies have explored their effects on the TME. In this review, we report the effects of 29 single herb medicines or herbal formulas on the TME, based on the findings of 64 published studies. Specifically, we describe the effects of these herbal medicines on cancer-associated fibroblasts/tumor-associated fibroblasts, tumor-associated endothelial cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Among the reviewed herbal medicines, the most promising TME-modulating effects were exhibited by curcumin, DHA, EGCG, resveratrol, and silibinin; these medicines showed the ability to regulate two or more components of the TME. The findings of this review support the notion that the combination of herbal medicines with conventional anticancer therapies are likely to exhibit a clinical benefit, which should be further explored in clinical trials.

Combating Drug Resistance in Colorectal Cancer Using Herbal Medicines.

Colorectal cancer (CRC) is one of the most prevalent and lethal cancer types around the world. Most of the CRC patients are treated with chemotherapeutic drugs alone or combined. However, up to 90% of metastatic cancer patients experience the failure of treatment mostly because of the acquired drug resistance, which can be led to multidrug resistance (MDR). In this study, we reviewed the recent literature which studied potential CRC MDR reversal agents among herbal medicines (HMs). Among abundant HMs, 6 single herbs, Andrographis paniculata, Salvia miltiorrhiza, Hedyotis diffusa, Sophora flavescens, Curcuma longa, Bufo gargarizans, and 2 formulae, Pien Tze Huang and Zhi Zhen Fang, were found to overcome CRC MDR by two or more different mechanisms, which could be a promising candidate in the development of new drugs for adjuvant CRC chemotherapy.

The Survival Benefit of Combination Therapy With Mild Temperature Hyperthermia and an Herbal Prescription of Gun-Chil-Jung in 54 Cancer Patients Treated With Chemotherapy or Radiation Therapy: A Retrospective Study.

Background: The combination of herbal medicine with conventional treatment increases the survival rate of cancer patients, but the effect is not great. Hyperthermia may have a synergistic effect with herbal medicine alongside conventional medicine. Objective: To monitor the efficacy of hyperthermia together with Gun-Chil-Jung (GCJ) capsule for event-free survival (EFS) and overall survival (OS) for the treatment of various cancers. Methods: We collected data retrospectively on 54 cancer patients of all stages. They were divided into 4 groups according to each hyperthermia or GCJ treatment period. Hyperthermia with 0.46 MHz radiofrequency wave was applied a power of 50 to 100 W for 70 minutes. GCJ capsules were administered orally 3 times a day. Results: The median follow-up was 13.4 months, and 25 (55.6%) patients showed disease-related events. Hyperthermia with GCJ treatment was administered in combination group (n = 36, 66.7%) and traditional Korean medicine-only group (n = 17, 31.5%). The median EFS was 190 days, and the median OS was 390 days. The group of hyperthermia 7 times or fewer and GCJ more than 28 days showed longer EFS and OS. The analysis of superiority between hyperthermia and GCJ showed no significant difference (EFS, P = .55; OS, P = .364). Conclusions: The combination of hyperthermia 1 to 2 times a week with GCJ treatment may improve survival of cancer patients treated or being treated with conventional cancer therapies.

Synergistic hepatoprotective effects of CGplus on CCl4-induced acute injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese/Korean medicine suggests "blood stasis ()", "stagnation of vital energy ()" and "dampness and Phlegm ()" as the main etiologies of liver disorders, and multiherbal formulas are generally believed to exert synergistic action. AIM OF THE STUDY: The present study aimed to investigate the synergistic hepatoprotective effects of CGplus (a mixture of Salviae miltiorrhiza, Artemisia iwayomogi and Ammomum xanthioides) compared to those of the individual herbs. METHODS AND MATERIALS: A total of fifty-six male Balb/C mice were randomly divided into eight groups and were administered water (normal and CCl4 groups), 100 mg/kg S. miltiorrhiza, A. iwayomogi, or A. xanthioides, 50 or 100 mg/kg CGPlus or dimethyl dimethoxybiphenyl dicarboxylate (DDB) as a positive control for 4 consecutive days. After a single CCl4 injection (i.p., 10 mL/kg of 0.2% CCl4 in olive oil), blood and liver tissues were collected after 18 h of fasting for serum biochemistry, histopathological examination and molecular analyses. RESULTS: CCl4 injection induced drastic hepatic injury characterized by a more than 30-fold increase in the release of AST and ALT into the serum. These alterations were significantly attenuated by pretreatment with each of the three herbs, while the effects of the individual herbs were synergistically augmented by CGPlus pretreatment. The synergistic hepatoprotective actions of CGPlus were demonstrated consistently by analyses of oxidative stress (oxidative stressors, oxidation products and antioxidant enzymes), pro-/anti-inflammatory cytokines (TNF-ɑ, IL-1ß, IL-6, IL-10), and apoptosis (caspase-3, p53 and BAX) and histopathology. CONCLUSIONS: These data suggest that CGPlus exerts its hepatoprotective effects in a synergistic manner, and further studies are required for clinical application using other chronic models.

Recovery from hepatitis A after Korean medicine-based treatment : a case report.

BACKGROUND: Many studies reported that Korean medicine (KM) is effective for treating liver disease, including hepatitis A. However, KM, specifically with herbal medicine (Chungganplus, CGP) has not been reported yet. We aimed to report a patient with hepatitis A who was treated with KM including CGP, acupuncture, and moxibustion for 12 days. METHODS: A 39-year-old man with hepatitis A who was hospitalized for 12 days after being admitted to our hospital with abdominal pain, diarrhea and vomiting. We prescribed CGP three times a day, with acupuncture performed twice daily and moxibustion at conception vessel (CV)-12 once a day. Follow-up blood tests have been done 4 times during the admission in order to access the effect of the treatment. RESULTS: In 12 days the symptoms had disappeared and the blood test results improved steadily. His AST level have declined from 1,189 IU/L to 44 IU/L, ALT from 2,423 IU/L to 127 IU/L, r-GTP from 1,347 IU/L to 339 IU/L, ALP from 384 IU/L to 205 IU/L, and total bilirubin from 3.6 mg/dL to 0.89 mg/dL. CONLCUSIONS: This case suggests that KM-based treatment using CGP may be effective for hepatitis A with no adverse effect. Further research and clinical trial on CGP would be needed to make the basis more valid.

Successful treatment of refractory edema with traditional herbal medicine: A case report.

RATIONALE: Refractory edema is characterized by persistent swelling which does not react to diuretic use and sodium restriction. Traditional herbal medicine, Gwack Rhyung Tang and Chunggan extract effectively treated refractory lower limb edema caused by cirrhosis and improved liver function. PATIENT CONCERNS: A 64-year-old male patient with a history of hypertension, diabetes mellitus, hepatic encephalopathy, and cellulitis presented lower limb edema which did not react to diuretics for more than 7 months. DIAGNOSES: Refractory edema caused by cirrhosis. INTERVENTIONS: The patient was treated for 25 days using Gwack Rhyung Tang and Chunggan extract. OUTCOMES: Loss of body weight, decrease in circumferences of both lower limb and improvement of liver function biochemistry results are checked. There was no recurrence or aggravation of the condition up to 3 weeks of follow-up periods. LESSONS: Traditional herbal medicine can be an effective alternative for refractory edema due to cirrhosis with improving liver function.

Overcoming P-Glycoprotein-Mediated Multidrug Resistance in Colorectal Cancer: Potential Reversal Agents among Herbal Medicines.

OBJECTIVES: Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colorectal cancer (CRC), and the primary determinant of MDR in CRC patients is active drug efflux owing to overexpression of P-glycoprotein (P-gp) in cancer tissues. Despite research efforts to overcome P-gp-mediated drug efflux, the high toxicity of P-gp inhibitors has been a major obstacle for the clinical use of these agents. The aim of this study was to review the literature for potential P-gp reversal agents among traditional herbal medicines, which offer the advantages of safety and potential synergetic effects in CRC chemotherapy. METHODS: We searched ten databases including 3 English databases, 1 Chinese medical database, and 6 Korean medical databases up to July 2018 and included in vivo and in vitro studies evaluating the effects of herbal medicines as P-gp reversal agents in CRC. RESULTS: A total of 28 potentially related studies were identified and 16 articles were included. Involving 3 studies about Salvia miltiorrhiza and 2 studies about Curcuma longa, finally we found 14 kinds of traditional herbal medicines-Salvia miltiorrhiza, Curcuma longa, Sinomenium acutum, Stephania tetrandra, Bufo gargarizans, Coptis japonica, Piper nigrum and Piper longum, Hedyotis diffusa, Schisandra chinensis, Glycyrrhiza glabra, Glycyrrhiza inflate, Daphne genkwa, Stemona tuberosa Lour, and Andrographis paniculata-as showing efficacy as P-gp inhibitors in anticancer drug-resistant CRC cells in vitro and in vivo. CONCLUSIONS: This brief account provides insight into the relationship between P-gp and CRC. Further studies on herbal medicines with demonstrated effects against P-gp overexpression will aid in improving the efficacy of chemotherapy in CRC.

Patient With Unresectable Cholangiocarcinoma Treated With Radiofrequency Hyperthermia in Combination With Chemotherapy: A Case Report.

Hyperthermia, which is a noninvasive treatment that causes tumor cells to become heated and that works in synergy with anticancer drugs and radiation therapy, is emerging as a promising treatment for patients with cancer. The purpose of this study is to report the efficacy of hyperthermia combined with chemotherapy (gemcitabine/cisplatin) for the treatment of a patient with unresectable cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with chemotherapy. However, because the treatment with radiation and chemotherapy was not successful, he decided to undergo hyperthermia combined with chemotherapy as a second treatment option. He was suffering from fatigue, dyspepsia, epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was administered 32 times over a period of 4 months. The patient experienced no critical complications, and the patient's condition improved, with the carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being relatively lowered. In addition, the computed tomography scan showed that the cholangiocarcinoma had not progressed. In conclusion, this case report suggests radiofrequency hyperthermia combined with chemotherapy may be a promising treatment option for patients with unresectable cholangiocarcinoma.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.

Anti-Fatigue Effects of Enzyme-Modified Ginseng Extract: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Ginseng saponin is known to have biological activities in maintaining homeostasis and enhancing vital energy. Enzyme-modified ginseng extract (EMGE) was designed to increase the content of its active constituents and to intensify biological activity. The present study investigated the anti-fatigue effects of EMGE in healthy adults in a randomized, double-blind, placebo-controlled trial. DESIGN: Fifty-two healthy subjects met the diagnostic criteria and were randomly allocated into one of two groups: EMGE (2,000 mg/day) or placebo. EMGE or placebo were administered to each group for 4 weeks. Fatigue scores using the Visual Analogue Fatigue Scale (VAFS) and Revised Piper Fatigue Scale (RPFS) were considered as the primary outcome measure. Life-quality scores were investigated using the Short-Form Health Survey (SF-36). The safety and adverse effects of EMGE were also assessed. RESULTS: A repeated-measures analysis of variance showed that there was a significant difference in the VAFS scores VAFS between the treatment and placebo groups after 4 weeks. The treatment group's score decreased more than that of the placebo group. There was no difference in the RPFS and SF-36 scores between the two groups. There were no fatal adverse effects. CONCLUSION: EMGE treatment for 4 weeks decreased fatigue severity in a healthy population. Adverse effects were rare, and EMGE was generally well tolerated. Randomized, placebo-controlled trials of EMGE are justified in order to elucidate the underlying mechanism of EMGE in combating fatigue.

Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer.

ABSTRACT: Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC. Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.

Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial.

UNLABELLED: The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day(-1)) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4 ± 5.0 to 15.1 ± 6.5 [95% CI 2.3 ~ 8.2] for 1 g and 20.7 ± 6.3 to 13.8 ± 6.2 [95% CI -0.1 ~ 4.2] for 2 g compared with placebo 20.9 ± 4.5 to 18.8 ± 2.9 [95% CI 4.1 ~ 9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3 ± 1.3 to 4.4 ± 1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1 ± 1.0 to 5.8 ± 1.3 [95% CI 2.2 ~ 3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0000048.

Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: randomized, double blind, placebo-controlled clinical trial with parallel design.

OBJECTIVE: To examine the efficacy of Korean red ginseng for improving blood flow in healthy people. METHODS: Participants were randomized and treated with 1500 mg of Korean red ginseng extract or placebo for 8 weeks. The effect of Korean red ginseng was evaluated by digital infrared thermal images, and Doppler sonography, and blood test. RESULTS: Forty subjects completed the protocol. Imbalance in local thermal distribution was significantly decreased in the Korean red ginseng group confirmed by digital infrared thermal images. Doppler sonography showed no significant change in maximum and average rates of blood circulation in single or complex areas. Blood analyses for coagulation and lipid metabolism factors revealed no significant changes. No abnormal reactions to the Korean red ginseng were observed. CONCLUSION: Digital infrared thermal imaging showed that the temperature deviation in the whole body decreased safely in the Korean red ginseng group, which mitigated the body-temperature imbalance. This result suggests that the Korean red ginseng improves blood circulation in the human body.

Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers.

OBJECTIVES: Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. METHODS: This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. RESULTS: Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. CONCLUSIONS: P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product.