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Despite an increase in the survival rate of patients with cancer owing to the use of current chemotherapeutic agents, adverse effects of cancer therapies remain a concern. Combination therapies have been developed to increase efficacy, reduce adverse effects, and overcome drug resistance. Genipin is a natural product derived from Gardenia jasminoides, which has been associated with anti-inflammatory, anti-angiogenic, and anti-proliferative effects; hypertension; and anti-ischemic brain injuries. However, the enhancement of oxaliplatin sensitivity by genipin remains unexplored. Our study showed that a combination of genipin and oxaliplatin exerts synergistic antitumor effects in vitro and in vivo in colorectal cancer cell lines through the reactive oxygen species (ROS)/endoplasmic reticulum (ER) stress/BIM pathway. Importantly, the combination did not affect normal colon cells. BIM knockdown markedly inhibited apoptosis induced by the combination. In addition, genipin induced ROS by inhibiting superoxide dismutase 3 activity. These findings suggest that genipin may be a novel agent for increasing the sensitivity of oxaliplatin against colorectal cancer. The combination of oxaliplatin and genipin hold significant therapeutic potential with minimal adverse effects. ©2019 American Association for Cancer Research.

Zhi-Zi-Hou-Po decoction (ZZHPD) is one of the famous antidepressant Chinese formulas and is composed of Magnolia officinalis cortex (HP), Gardenia jasminoides Ellis (ZZ) and Citrus aurantium L. (ZS). Magnolol (MN) and honokiol (HN) from HP are the major active ingredients responsible for the therapeutic effects of ZZHPD. The aim of this study is to compare the pharmacokinetics and rat brain distribution of MN and HN after oral administration of HP extract and its compatibility with other herbal medicines in ZZHPD by HPLC-FLD. Compared with the HP group, Tmax (time to reach peak drug concentration in plasma) and AUC(0-τ) significantly increased in the ZZHPD and HP-ZZ groups. There was little change in the HP-ZS group in comparison with the HP group, which indicated that ZZ promotes absorption extent and defers the absorption rate of MN. The different compatibility of ZZHPD had a different degree of impact on the concentration of MN and HN in brain. The concentration of MN significantly increased in the HP-ZZ group while it decreased in the HP-ZS group compared with the HP group, which explained the concentration of compounds being slightly greater in the ZZHPD group than in the HP group. HP mixed with other medicines resulted in a decrease in HN concentration in the brain, particularly HP compatible with ZS. The results could be helpful for revealing the compatibility mechanism and providing clinical medication guidance for ZZHPD.

Genipin is obtained from the fruit of Gardenia jasminoides Ellis and acts as an herbal medicine or functional food in East Asia. In addition to produce natural colorant, it possesses widely antiinflammatory, antithrombotic, antidepressive and anticarcinogenic activities. However, little research focuses on the potential of genipin for drug-drug interactions. In this study, effects of genipin on mRNA and protein expression of cytochrome P450 (CYP) 2C19, CYP2D6 and CYP3A4 were detected by real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) and Western blot, respectively, in human hepatoma HepG2 cells. Enzyme activities of which were detected by luminogenic CYP assay in vitro. Moreover, effect of genipin on P-glycoprotein expression was analyzed by Western blot. Results showed that genipin possessed a significant induction on CYP2D6 and a remarkable inhibition on CYP2C19 and CYP3A4 not only from the expression of mRNA and protein (P<0.05 or P<0.01), but the level of enzyme activity. Moreover, a concentration-dependent induction of genipin on P-glycoprotein expression was observed. In conclusion, caution should be exercised with respect to the induction or inhibition of genipin on CYP isoenzymes and the strong induction on P-glycoprotein.

Zhi-Zi-Hou-Pu decoction (ZZHPD), a classic antidepressant formula, is composed of Gardenia jasminoides Ellis (ZZ), Fructus aurantii immaturus (ZS) and Cortex magnoliae officinalis (HP). ZZHPD has attracted a great deal of attention for its antidepressant effects. The aim of this study was to compare the pharmacokinetics of geniposide (one of the predominant active ingredients) after oral administration of different combinations of ZZHPD and to explore the influence of herb-herb interaction on the pharmacokinetics of geniposide. Twenty four rats were divided randomly into four groups and were administered one of the four extracts: ZZ, ZZ-HP, ZZ-ZS and ZZHPD (ZZ-HP-ZS) via intragastric gavage with approximately the same dose of 40.65 mg/kg geniposide (an effective human daily dose of ZZHPD). Plasma concentrations of geniposide were determined using an HPLC method. Pharmacokinetic parameters were calculated from the plasma concentration-time data. Compared with ZZ alone, the ZZ-ZS combination delayed T(max) and ZZ-HP, ZZ-ZS, ZZHPD remarkably shortened the T(1/2) of geniposide. In addition, ZZ-HP, ZZ-ZS, ZZHPD obviously increased the AUC of geniposide. The result illustrated that the oral bioavailability of geniposide was dramatically enhanced when ZZ was combined with HP or/and ZS. It can be deduced that herb-herb interaction may increase the absorption, and significantly improve the oral bioavailability of geniposide in rats.

Crocetin is a carotenoid isolated from the seeds of Cape jasmine (Gardenia jasminoides). The cytotoxicity and DNA-adduct formation of rat microsome-activated aflatoxin B1 (AFB1) in the C3H10T1/2 cells were significantly inhibited by pretreatment of crocetin. Most significant inhibition was found at the time of 9 h after crocetin pretreatment. Under these experimental conditions, consistent elevation in the cytosolic glutathione (GSH) levels and the activities of GSH S-transferase (GST) and GSH-peroxidase (GSH-Px) were observed. Crocetin treatment also resulted in a decrease in AFB1-DNA adduct formation in vitro, while no effect of crocetin on the formation of AFB1-8,9-oxide in vitro system was detected as measured by the Trisdiol method. From these results, we suggested that the protective effect of crocetin on the AFB1-cytotoxicity in C3H10T1/2 cells might be due to the cellular defense mechanisms that elevated the cytosol GSH and the activities of GST and GSH-Px.

14. Carcinogenesis. 1986 Apr;7(4):595-9. doi: 10.1093/carcin/7.4.595. Protection of crocin dyes on the acute hepatic damage induced by aflatoxin B1 and dimethylnitrosamine in rats. Lin JK, Wang CJ. Chemopreventive agents are compounds that inhibit carcinogenesis when administered prior or subsequent to a course of carcinogen administration. The effects of dietary administration of crocin dyes on the hepatic damage induced by aflatoxin B1 (AFB1) and dimethylnitrosamine (DMN) in rats were investigated. Female Sprague-Dawley rats were treated with different dosages of AFB1 (0.9 or 4.5 mg/kg) or DMN (8 or 20 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and lactic dehydrogenase. Pre-treatment of the animals with crocin dyes 50 mg/kg daily for three consecutive days, the enzyme elevations were significantly suppressed. This suggested that the crocin dyes possessed chemopreventive effects on the early acute hepatic damage induced by AFB1 or DMN. Feeding experiments demonstrated that crocin dyes at 0.1% in the diet could suppress partially the chronic hepatic damage induced by multiple dosages of AFB1 or DMN, but at a higher concentration of 1% crocin dye failed to do so because of their host toxicity. Crocin dyes are extracted from the fruits of Gardenia jasminoides and consist of carotenoids and geniposides as active principles. The protective mechanisms of crocin dyes may be attributed to their carotenoids which are converted metabolically to retinoids in rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, joint destruction, and systemic immune dysregulation. Geniposide, an iridoid glycoside derived from Gardenia jasminoides, has shown promising anti-inflammatory and immunomodulatory properties in preclinical studies. This meta-analysis aims to systematically evaluate the therapeutic efficacy and mechanistic pathways of Geniposide in experimental animal models of RA. A comprehensive literature search was conducted using Google Scholar, Science Direct, and PubChem up to June 2025. In vivo studies assessing the effects of Geniposide on arthritis-related outcomes in RA-induced rodent models were included. Data were extracted and analyzed using RevMan 5.4. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. The SYRCLE Risk of Bias tool was used for quality assessment to assess publication bias. Fourteen eligible studies were involved in quantitative synthesis. Geniposide significantly reduced arthritis score, paw swelling, and histopathological joint damage. Pro-inflammatory cytokines IL-6, IL-17, TNF-α, and IL-1β were markedly suppressed, while anti-inflammatory cytokines IL-10 and IL-4 were up-regulated. Mechanistically, Geniposide acted through modulation of NF-κB, MAPK, PTEN/PI3K, and Wnt/β-catenin pathways in reported studies. Geniposide exhibits potent anti-arthritic effects in RA animal models by modulating inflammatory cytokines. These findings highlight its therapeutic potential as a candidate for RA treatment; however, further clinical studies are needed to validate its safety and efficacy in humans. © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well do

BACKGROUND: Yinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation. PURPOSE: To systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions. RESULTS: A total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI = 0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis. CONCLUSION: Yinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effectiv

This study reviewed the biological action of key herbs and evaluated systematically the efficacy and safety of oral Gentiana formula for herpes zoster (HZ). Experimental studies relevant to HZ were identified in PubMed. Randomized controlled trials using Gentiana formula for HZ were identified from nine English and Chinese databases. The primary outcome was evaluation of pain. Potential risk of bias was assessed. Meta-analysis was conducted using mean difference or risk ratio with 95% confidence intervals. Key herbs Gentiana scabra Bunge, Gentiana triflora Pall, Scutellaria baicalensis Georgi, and Gardenia jasminoides Ellis have shown antiinflammatory actions through inhibition of inflammatory cytokines and pro-inflammatory enzymes. Twenty-six clinical studies, involving 2955 participants, were included. Modified Gentiana formula resolved pain earlier than pharmacotherapy when used alone or combined with topical Chinese herbal medicine. Incidence of postherpetic neuralgia was lower (risk ratio 0.14, 95% confidence interval 0.03 to 0.74) with modified Gentiana formula plus topical Chinese herbal medicine. Mild adverse events were reported. Antiinflammatory actions of key herbs of Gentiana formula may explain clinical benefit in hastening pain relief and decreasing postherpetic neuralgia. Few adverse events were reported. Findings were limited by study quality and diversity in intervention and comparator dosage. Copyright © 2017 John Wiley & Sons, Ltd.