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BACKGROUND: The immune-enhancing effects of red Platycodon grandiflorus root extract (RPGE) has been reported in vitro and in vivo, but there are few studies on humans. Therefore, this study aimed to investigate the efficacy and safety of RPGE in enhancing immune function in healthy subjects. SUBJECTS AND METHODS: An 8-week randomized, double-blind, parallel, placebo-controlled clinical trial was conducted at the Gachon University Gil Medical Center, Incheon, South Korea. A total of 100 adults aged 20-75 years with white blood cell counts of 3000-10,000 cell/µL were randomly divided into two groups (RPGE group, 50 and placebo group, 50) using a computer-generated random list with a 1:1 allocation ratio. The subjects consumed RPGE (2 times/day, 2 tablets/time, 375 mg RPGE powder/tablet) or placebo for 8 weeks. All test foods for the human study were coded and administered under double-blind conditions. The primary outcome was a change in the NK cell activity after 8 weeks of treatment compared to the baseline. RESULTS: Among 100 subjects enrolled for the study, 87 completed the study. NK cell activity (p = 0.005) and IFN-γ level (p = 0.003) of the RPGE group (n = 41) were higher than those of the placebo group (n = 46). The findings of the safety assessment revealed absence of clinically significant changes in any test and serious adverse events throughout the study. CONCLUSION: In conclusion, these results demonstrate the efficacy and safety of RPGE, suggesting it to be a beneficial agent for enhancing immune function in humans. TRIAL REGISTRATION: CRIS Registration Number KCT0005945, https://cris.nih.go.kr.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Cisplatin, a widely used chemotherapeutic agent, exerts its anticancer effect by inducing DNA damage, and inhibiting transcription and replication. However, its repeated administration can lead to severe side effects and the development of drug resistance, thereby limiting its clinical efficacy. Thus, novel combination strategies are urgently needed to enhance the anticancer effects of cisplatin. The present study aimed to investigate the potential of Platycodin D (PD), a natural saponin extracted from Platycodon grandiflorus, to enhance cisplatin sensitivity in HNSCC cells. The results demonstrated that combination treatment with PD and cisplatin synergistically reduced cell viability and markedly suppressed colony formation compared with either agent alone. Furthermore, the combination treatment markedly increased intracellular reactive oxygen species (ROS) levels, and markedly downregulated the expression levels of antioxidant genes, including heme oxygenase‑1, NAD(P)H quinone dehydrogenase 1, superoxide dismutase 1 and sulfiredoxin 1. Additionally, the combination treatment excessively activated autophagy, whereas PD inhibited autophagic flux, as determined by LC3A/B and p62 accumulation following Bafilomycin A1 treatment, ultimately promoting apoptosis. These findings suggested that PD may serve as a potential cisplatin sensitizer by enhancing ROS accumulation and disrupting autophagy, thereby presenting a promising combination therapeutic strategy for the treatment of HNSCC.

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.

Cisplatin (DDP) is a first-line drug for non-small cell lung cancer (NSCLC), but its efficacy and applications are constrained by intolerance and serious side effects. Platycodon grandiflorus (PG) is usually used as lung medicinal drug to enhance other drug's effect on lung diseases. Therefore, present study aim to investigate anti-NSCLC effect of PG with DDP and mechanism involved in the combination for the first time. The results showed that compared with DDP group, the combined groups (DDP combined with 1, 2 and 4 g/kg of PG) reduced the tumor luminescence density by 26.0%, 78.2% and 32.8% respectively, and decreased the death rates, lung index, pathological damage and inflammation in lung tissue. Protein analysis of lung tissue showed that its anticancer effect may be associated with tumor cell apoptosis. Therefore, vitro studies showed that PG combined with DDP down-regulated the expression of p-Akt and PI3K and improved the protein expression of cleaved-caspase 9 in A549 cell and PG promotes the apoptosis of DDP and these mechanisms were related by inhibition of the PI3K/Akt signaling pathway. Our study confirms that the combination of PG and DDP will help enhance efficacy of DDP and is important for improving platinum-based chemotherapy.

Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20-60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.

Background: In clinical practice, antibiotics and/or inhaled or oral hormone preparations are the first line of treatment for chronic pharyngitis. However, this therapeutic regimen is not satisfactory enough. At present, medicinal plants as dietary supplements or functional foods are widely recognized for the treatment and prevention of different diseases. Purpose: This study aimed to evaluate the efficacy of the botanical lozenge made from several medicinal plant extracts in the treatment of chronic pharyngitis and its effects on patients' illness perception and adherence to treatment. Methods: Patients with chronic pharyngitis were randomly assigned to the experimental group (n = 52) or the control group (n = 51). Patients were given botanical lozenges prepared from the extracts of medicinal plants such as Siraitia grosvenorii (Swingle) C. Jeffrey ex A.M.Lu and Zhi Y. Zhang [Cucurbitaceae; Siraitiae fructus], Lonicera japonica Thunb [Caprifoliaceae; Lonicerae japonicae flos], Platycodon grandiflorus (Jacq.) A. DC [Campanulaceae; Platycodon radix], and Glycyrrhiza uralensis Fisch. ex DC [Fabaceae; Glycyrrhizae radix et rhizoma] or placebos made of starch for 15 days. The improvement of pharyngeal symptoms and signs, illness perception, and adherence to treatment were evaluated at the end of the intervention. Results: The total score of pharyngeal symptoms of patients in the experimental group (3.33 ± 2.33) was significantly lower than that in the control group (5.20 ± 2.93) (p < 0.01). In comparison to the control group (3.43 ± 1.43), the total pharyngeal signs score of patients in the experimental group (2.69 ± 1.59) was considerably lower (p < 0.01). The improvement rates of pharyngeal itching, dry throat, pharyngeal foreign body sensation, aggravation due to excessive speaking, and congestion of pharyngeal mucosa in the experimental group were 73.81%, 67.50%, 67.57%, 65.22% and 44%, respectively, which were significantly higher than those in the control group (p < 0.05). In addition, patients taking botanical lozenges had better illness perception and adherence to treatment than those taking placebos (p < 0.05). Patients with low adherence to treatment showe

The purpose of this study was to evaluate the effects of dietary Chinese medicinal herbs (CMH) supplementation composed of Panax ginseng, Dioscoreaceae opposite, Atractylodes macrocephala, Glycyrrhiza uralensis, Ziziphus jujube and Platycodon grandiflorum, on the performance, intestinal tract morphology and immune activity in weanling pigs. Two hundred and forty weaned pigs were assigned randomly to four dietary groups including the negative control (basal diet), 0.1% CMH, 0.3% CMH and 0.114% antibiotic (Chlortetracycline calcium Complex, Sulfathiazole and Procaine Penicillin G) supplementation groups for a 28-day feeding trial. Results indicated that both CMH supplementation groups had a better gain and feed/gain than control group (CT) during the first 2 weeks of the experimental period. The 0.3% CMH had a significant decrease in the diarrhoea score in first 10 days of experimental period when compared with other groups. The CMH supplementation groups had a higher villous height, increased lactobacilli counts in digesta of ileum and decreased coliform counts in colon compared with CT. The immune activities of polymorphonuclear leucocytes (PMNs), including the respiratory burst and Salmonella-killing ability, were significantly enhanced in CMH supplementation groups at day 7 of experiment period. The CMH and antibiotic supplementations increased the nutrient digestibility such as dietary dry matter, crude protein and gross energy in weanling pigs. In conclusion, the dietary CMH supplementation improved intestinal morphology and immune activities of PMNs, thus giving rise to nutrient digestibility and reduce diarrhoea frequency in weanling pigs. © 2011 Blackwell Verlag GmbH.

The application of fertilizers is a key agronomic practice in the artificial cultivation of medicinal plants, aiming to boost yields and enhance the levels of their bioactive constituents. However, systematic investigations on the influence of various fertilizers on the concentration of active compounds in saponin-containing medicinal plants remain insufficient. In this study, 966 experimental outcomes from 29 papers were analyzed via meta-analysis to examine the effects of organic fertilizers, inorganic fertilizers, and their combined application on the levels of different saponin monomers in medicinal plants. The findings from the meta-analysis revealed that inorganic fertilizers contribute positively to the accumulation of saponins such as Rg1 in ginseng, Rb1, Rc, Rd, Re, and Rg1, in addition to the saponins from Paris polyphylla, Dioscorea, Panax quinquefolius, and Platycodon grandiflorus. Moreover, the application of organic fertilizers was found to markedly elevate the concentrations of Notoginsenoside R1, Ginsenoside Rb1, Ginsenoside Rb2, Re, and Rg1, along with Lancemasid saponins and Quinoa saponins. The combined use of both organic and inorganic fertilizers was shown to effectively increase the levels of Notoginsenoside R1 and Panax ginsenosides, encompassing Rb1, Rb2, Rc, Rd, Re, and Rg1. Overall, the results suggest that both individual and combined applications of organic and inorganic fertilizers have a positive impact on the enhancement of saponin monomers in medicinal plants. However, inorganic fertilizers promote the increase of saponin content, their prolonged use may lead to soil compaction and acidification, which could compromise the yield and quality of medicinal plants. On the other hand, organic fertilizers improve the soil environment and stimulate saponin accumulation, they do not supply all the nutrients required for the sustained growth of these plants. Therefore, a balanced fertilization strategy combining both organic and inorganic fertilizers is recommended as the optimal approach for cultivating saponin-rich medicinal plants.

Objectives: Kikyo-to (Kt), a herbal medicine composed of glycyrrhiza root (Chinese licorice) and Platycodon root extracts (Chinese bellflower), is commonly used in Japan for relief of throat symptoms related to acute upper respiratory tract infection (URTI). Its effectiveness on URTI-associated sore throat pain over 30 min is examined here in comparison with a placebo. Design: Randomized double-blinded multicenter trial. Settings/Location: Two local Japanese medical centers with primary care. Subjects: Patients aged 20-65 years with URTI-related sore throat. Interventions: Patients were randomized to receive either 2500 mg of Kt, or 2500 mg of placebo (lactose). Randomization was stratified by age (< 45 vs. ≥ 45 years) and baseline sore throat score according to visual analogue scale (VAS) (< 50 vs. ≥ 50). Outcome measures: Primary outcome was change to sore throat score according to VAS 30 min after administration of Kt. Perceived impact of the sore throat on daily life at 30 mins after administration was another outcome. Outcomes are analyzed in the intention-to-treat population. Results: Among 70 participants, (Kt group: 36; placebo group: 34), each group contained 34 patients for analysis (n = 68, total). Difference between the groups in the mean change of sore throat score according to VAS at 30 min was without statistical significance (Kt 15.3, placebo 17.2; p = 0.66). Patients reporting that their sore throat had a moderate or greater impact on daily life were also similar in proportion between the groups (Kt 61.8% vs. placebo 55.9%; p = 0.80). Side effects were not reported. Conclusions: Kt did not relieve acute URTI-associated sore throats significantly more than a placebo. (UMIN trial ID: UMIN000035591).

Background: Anthracycline-based chemotherapy is an effective treatment used for early-stage breast cancer patients. However, anthracycline use is limited due to its cardiotoxic effects. Recent studies have shown that Platycodon grandiflorum (PG) protects the heart from anthracycline-induced cardiotoxicity. However, no randomized, placebo-controlled clinical trial has been performed to investigate the clinical use of PG to prevent anthracycline-induced cardiotoxicity. This study aimed to evaluate the cardioprotective effects and safety of PG in early breast cancer patients receiving anthracycline-based chemotherapy. Methods: A total of 125 early breast cancer patients receiving anthracycline-based chemotherapy were enrolled and randomized into a PG group or placebo group in a 1:1 ratio. Results: Only 2 (3.1%) participants in the placebo group and 1 (1.6%) participant in the PG group experienced NYHA (New York Heart Association) class III or IV heart failure. There were no significant differences observed between the 2 groups. However, compared with the placebo group, patients in the PG group showed a lower incidence of subclinical heart failure (21.9% vs 8.2%, respectively, P = .033), as well as lower cardiac troponin T levels (48.4% vs 31.1%, respectively, P = .002). Importantly, there were no differences observed in the antitumor effects of anthracycline between the 2 groups (disease-free survival: hazards ratio = 1.09, 95% confidence interval = 0.45-2.62, P = .84; overall survival: hazards ratio = 1.46, 95% confidence interval = 0.33-6.43, P = .62). Conclusion: PG prevents anthracycline-induced acute and chronic cardiac injury in early-stage breast cancer patients without compromising the antitumor effects of chemotherapy.

Traditional Chinese Medicine (TCM) is widely used in the treatment of Mycoplasma pneumoniae Pneumonia (MPP) in East Asia. However, our current understanding of the underlying molecular mechanism remains dispersive and promiscuous. In this study, a systematic pharmacological approach combined with literature data mining was applied for drug similarity evaluation, drug half-life evaluation, oral bioavailability prediction, drug target exploration, Gene Ontology (GO) analysis, KEGG pathway enrichment and network construction, thus providing the rationale for its clinical performance. Five mostly studied herbs, including Ephedra Herba, Amygdalus communis Vas, Platycodon grandiforus, Licorice and Scutellariae Radix, were selected from the literature. Total ninety-three active ingredients, which are expected to be the effective components for MPP treatment, were screened out. Interrelationship between active compounds, drug targets and signaling pathways were analyzed to reveal the therapeutic effect of TCM in detail. Of importance, we found that TNF, β2AR and PTGS2 play pivotal role in TCM mediated MPP inhibition. And mechanistically, epithelial apoptosis (defensive barrier function), GPCR signaling (symptom amelioration) and immune pathways (innate signaling and adaptive Th17 response) are critically involved. Our work, achieved through systematic pharmacology and data mining, enlarges the knowledge of TCM in MPP therapy, and could provide valuable insights for further drug discovery studies.

Objective Kikyo-to (KKT) is a fixed combination of glycyrrhiza root and platycodon root extracts. It is an herbal medicine traditionally used in Japan for relieving sore throat associated with acute upper respiratory tract infection (URTI). No controlled studies have yet demonstrated its effect, however. We investigated the efficacy of KKT on sore throat associated with acute URTI. Methods Patients with sore throat who were diagnosed with URTI at the General Medicine Department Office, Akashi Medical Center Hospital, between December 2017 and May 2018 were enrolled. Participants were randomly assigned to two groups at a 1:1 ratio, with stratification by age and sore throat score on a Visual Analogue Scale (VAS), to receive 2.5 g of either KKT or a placebo. Participants and investigators were blinded to group allocation. The primary outcome was the change in sore throat score on VAS 10 minutes after KKT administration. Secondary outcomes were the impact of the sore throat on daily life (none, mild, moderate, and severe) at 10 minutes after administration. Results Thirty-five participants were assigned to each group (n=70, total). The difference in the mean change of sore throat score according to VAS within 10 minutes between the two groups was not statistically significant (KKT 14.40 vs. placebo 17.00; p=0.39). The proportion of patients with a moderate or greater impact of their sore throat on their daily life was also not significantly different between the groups (KKT 22.9% vs. placebo 40.0%; p=0.20). Patients reported no side effects. Conclusion KKT did not significantly relieve sore throat associated with acute URTI compared with placebo.

OBJECTIVE: To compare the difference in the therapeutic effect on post-infectious cough differentiated as wind-cold retention in the lung between the combined therapy of scraping and xuanfei zhisou decoction and the simple application of xuanfei zhisou decoction. METHODS: Eighty patients were randomized into a combined therapy group and a Chinese herbal medicine group, 40 cases in each one. In the Chinese herbal medicine group, the oral administration of xuanfei zhisou decoction was used. The main ingredients included roasted herba ephedrae, amygdalus communis vas, rhizoma zingiberis recens, platycodon grandiflorum, flos farfarae, pinellia temata, radix stemonae, herba periliae, etc., one dose a day, twice a day. In the combined therapy group, on the basis of the treatment as the Chinese herbal medicine group, scraping therapy was added and applied to the bladder meridian of foot-taiyang, the lung meridian of hand-taiyin, the conception vessel and the governor vessel, focusing on Tiantu (CV 22), Baihui (GV 20), Dazhui (GV 14), Feishu (BL 13), Fengmen (BL 12), Taiyuan (LU 9), Lieque (LU 7) and Fengchi (GB 20), once a week and one-week treatment as one session. Totally, the continuous two sessions were required in the two groups. The cough symptom score, cough remission time, relapse, TCM syndrome score, the score of Leicester cough questionnaire (LCQ), SP concentration in the supernatant of the induced sputum before and after treatment as well as clinical efficacy were observed in the two groups. RESULTS: The cough symptom score, TCM symptom score and SP concentration in the supernatant of the induced sputum were all apparently reduced after treatment in the patients of the two groups (all P<0.01). The scores in the combined therapy group were reduced in the higher amplitude as compared with those in the Chinese herbal medicine group (all P<0.01). The total effective rate was 95.0% (38/40) in the combined therapy group, better than 87.5% (35/40) in the Chinese herbal medicine group (P<0.05). Regarding the cough remission time and relapse rate, the results in the combined therapy group were better than those in the Chinese herbal medicine group[(5.3±1.2) d vs (7.4

BACKGROUND: Anthracyclines, alone or in combination with other drugs, are among the most effective chemotherapeutic agents to treat breast cancer both in the adjuvant and neoadjuvant setting. Unfortunately, anthracycline-associated dose-dependent cardiotoxicity is a limiting factor in clinical use. Extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity. However, most cardioprotective agents have shown little effect in clinical trials. Herbal medicines are pure, natural substances that have been used for centuries in many countries, including China. This trial aims to evaluate the cardioprotective effects and safety of Platycodon grandiflorum granules compared to placebo granules in patients with early breast cancer receiving anthracycline-based chemotherapy. METHOD/DESIGN: This study is a single-center, double-blinded, randomized, placebo-controlled, parallel-group trial. A total of 120 patients will be randomly allocated in a 1:1 ratio to receive either P. grandiflorum granules or placebo granules twice daily for 12 weeks. The primary outcome is heart failure (either clinical or subclinical). The secondary outcomes include all-cause mortality, cardiac death, electrocardiogram (ECG) findings, left ventricular diastolic function, longitudinal systolic strain and velocities measured by tissue Doppler imaging, cardiac biomarkers, such as troponin I (TnI), brain natriuretic peptide (BNP), and creatine kinase isoenzymes (CK-MB). Assessments will be performed at baseline (before randomization) and 3, 6, 9, 12, 16, and 20 weeks after randomization. DISCUSSION: This will be the first clinical trial to evaluate the cardioprotective effects and safety of P. grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. TRAIL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16009256 . Registered on 23 September 2016.