Fructus Gardenia Research Articles

Characterization of carbon dots from fructus gardeniae (Zhi-zi) and gardenia charcoal (black Zhi-zi) via microwave-assisted extraction

Characterization of carbon dots from fructus gardeniae (Zhi-zi) and gardenia charcoal (black Zhi-zi) via microwave-assisted extraction

Inhibition of compound action potentials in the frog sciatic nerve by inchinkoto, a traditional Japanese medicine used for oral mucositis

ObjectiveThis study aimed to determine the effects of traditional Japanese (Kampo) medicines used to treat oral mucositis on nerve conduction. MethodsThe effects of Kampo medicines, crude drugs, and chemical compounds on compound action potentials (CAPs) were analyzed using extracellular recordings in frog sciatic nerves. ResultsAmong the Kampo medicines, inchinkoto demonstrated the most significant reduction in CAP amplitude, with a half-maximal inhibitory concentration (IC50) of 5.4 mg/mL. Hangeshashinto, shosaikoto, hochuekkito, and juzentaihoto also showed a significant reduction. Regarding inchinkoto, Artemisiae Capillari Spica (artemisia) was the most effective crude drug, with an IC50 of 4.2 mg/mL for CAP amplitude reduction, whereas Gardeniae Fructus (gardenia) exerted no significant effect. However, the combined use of artemisia and gardenia reduced the CAP amplitude more effectively than artemisia alone, indicating a synergistic interaction. The chemical ingredient eugenol from artemisia administered at 1 and 3 mmol/L reduced CAP amplitude, whereas other chemical ingredients administered at 0.1 and 1 mmol/L had no significant effects. ConclusionsInchinkoto exhibited the most effective reduction in CAP amplitude in the sciatic nerve of frogs, primarily through the action of artemisia, with potential synergistic interaction between artemisia and gardenia.

The growth performance, anti-oxidative capacity, immunity and resistance to heat stress of abalone Haliotis discus hannai can be improved by a mixture of herbs

An 84-day feeding trial was carried out to assess the effects of dietary Chinese herbs mixture (CHM) on the growth performance, anti-oxidative capacity, immunity and resistance to heat stress of abalone Haliotis discus hannai. The CHM included, Scutellariae Radix (Scutellaria baicalensis, Gardeniae Fructus (Gardenia jasminoides), Artemisiae Scopariae Herba (Artemisia capillaris), Uncariae Ramulus Cum Uncis (Uncaria rhynchophylla), Polygoni Cuspidati Rhizoma et Radix (Polygonum cuspidatum). Six diets containing 0.00% (control group), 0.02%, 0.04%, 0.06%, 0.08% and 0.10% of CHM were formulated and fed to abalone (initial weight: 3.59 ± 0.03 g). The group with 0.04% of dietary CHM exhibited the highest weight gain rate (WGR), while the survival was not significantly affected by dietary CHM. The optimal level of dietary CHM for abalone was determined to be 0.049% on the basis of the quadratic regression model for WGR. Dietary CHM significantly elevated the activities of lipase, trypsin, cellulase, Na+/K+-ATPase, acid phosphatase, alkaline phosphatase and lysozyme and total anti-oxidative capacity. Besides, dietary CHM significantly reduced the malondialdehyde content and alanine amino transferase activity. The mRNA levels of cationic amino acid transporter 1 (cat1) and nuclear factor erythroid 2-related factor 2 (nrf2) were significantly up-regulated in the group with 0.04% of dietary CHM. While the mRNA levels of kelch-like ECH-associated protein 1 (keap1), nuclear factor-κb (nf-κb) and tumor necrosis factor-α (tnf-α) were decreased in dietary CHM supplemented groups. The glucose and cortisol content in the CFH and the falling rate of abalone were significantly lower in the CHM supplemented groups than that in the control group. In conclusion, dietary supplementation of CHM improved the growth performance, anti-oxidative capacity, immunity and the resistance to heat stress of abalone. The recommended level of CHM supplemented in diets for abalone was 0.049%.

Zhizi-Chuanxiong herb pair alleviates atherosclerosis progression in ApoE−/− mice by promoting the methylation of FGFR3 to inhibit MAPK/ERK-mediated apoptosis

Ethnopharmacological relevanceGardenia Fructus (Gardenia jasminoides Ellis, Zhizi) and Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., Chuanxiong) are both traditional Chinese medicines with vascular protective effects, which help detoxify and activate blood, and are clinically used to treat atherosclerosis (AS). Previously, Zhizi-Chuanxiong showed good efficacy in attenuating AS progression in rabbits. However, its potential mechanism is yet unclear. Aim of the studyThis study aimed to investigate the mechanism of the Zhizi-Chuanxiong herb pair (ZCHP) in attenuating AS progression from the perspective of DNA methylation. Materials and methodsAn AS mouse model was developed with ApoE−/− mice fed a high-fat diet (HFD). The therapeutic effects and mechanisms of ZCHP in treating HFD-induced AS were identified using an automated biochemical analyzer, enzyme-linked immunosorbent assays, histopathology, methyl-capture sequencing (MC-seq), pyrosequencing, quantitative reverse transcription-polymerase chain reaction (RT-qPCR), western blotting, and TUNEL staining. ResultsZCHP attenuated the development of AS by reducing lipid levels and enhancing the stability of plaques and via anti-inflammation. MC-seq and Kyoto Encyclopedia of Genes and Genomes analysis revealed that ZCHP corrected the expressions of both aberrant hypomethylated and hypermethylated genes, which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Protein–protein network interaction analysis and molecular docking showed that fibroblast growth factor 3 (FGFR3) and serine/threonine protein kinase (AKT1) were closely related to the MAPK signaling pathway among differentially methylated genes induced by ZCHP. Furthermore, pyrosequencing showed that ZCHP could induce FGFR3 hypermethylation and AKT1 hypomethylation in the promoter region, which was consistent with the MC-seq results. Molecular docking showed that the ZCHP was more tightly docked to FGFR3. Furthermore, RT-qPCR and western blotting showed that the mRNA and protein expression levels of FGFR3 decreased after treatment with ZCHP. Finally, western blotting showed that ZCHP suppressed the expression of phosphorylated MAPK and phosphorylated extracellular signal-regulated kinase (ERK), and TUNEL staining showed that ZCHP treatment could inhibit apoptosis in AS. ConclusionOur findings suggest that ZCHP can effectively attenuate AS progression by inhibiting MAPK/ERK signaling–mediated apoptosis via FGFR3 hypermethylation in the promoter region.

Gardenia jasminoides J. Ellis extract GJ-4 attenuates hyperlipidemic vascular dementia in rats via regulating PPAR-γ-mediated microglial polarization

BackgroundGJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.ObjectiveThis study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.DesignIn the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based on high-fat diet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD.ResultsOur results showed that GJ-4 could significantly reduce serum lipids level and improve cerebral blood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedly ameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotective effects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression.ConclusionOur results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.

Adverse Effects of Kampo Medicines.

This review summarizes the adverse effects of Kampo medicines. These adverse effects in terms of immunoallergic reactions include interstitial pneumonia, liver injury, allergic cystitis, and drug eruption. Many cases of interstitial pneumonia, liver injury, and allergic cystitis associated with Kampo formulas have been reported to be caused by formulas containing Scutellariae Radix (Scutellaria root, ogon). The known adverse effects linked to overdose of Kampo formulas include pseudoaldosteronism [caused by Glycyrrhizae Radix (licorice, kanzo)], sympathomimetic symptoms [caused by Ephedrae Herba (ephedra, mao)], aconite poisoning [caused by Aconiti Tuber (processed aconite root, bushi and uzu)], and diarrhea [caused by Rhei Rhizoma (rhubarb, daio)]. In recent years, mesenteric phlebosclerosis caused by the long-term administration of Gardeniae Fructus (gardenia fruit, sanshishi) has also been reported. It is necessary to consider these potential adverse effects when prescribing Kampo medicines in clinical practice.

GJ-4 ameliorates memory impairment in focal cerebral ischemia/reperfusion of rats via inhibiting JAK2/STAT1-mediated neuroinflammation

Ethnopharmacological relevanceGardenia jasminoides J. Ellis (Fructus Gardenia) is a traditional Chinese medicine with diverse pharmacological functions, such as anti-inflammation, anti-depression, as well as improvement of cognition and ischemia brain injury. GJ-4 is a natural extract from Gardenia jasminoides J. Ellis (Fructus Gardenia) and has been proved to improve memory impairment in Alzheimer's disease (AD) mouse model in our previous studies. Aim of the studyThis study aimed to evaluate the therapeutic effects of GJ-4 on vascular dementia (VD) and explore the potential mechanisms. Material and methodsIn our experiment, a focal cerebral ischemia and reperfusion rat model was successfully developed by the middle cerebral artery occlusion and reperfusion (MCAO/R). GJ-4 (10 mg/kg, 25 mg/kg, 50 mg/kg) and nimodipine (10 mg/kg) were orally administered to rats once a day for consecutive 12 days. Learning and memory behavioral performance was assayed by step-down test and Morris water maze test. The neurological scoring test was performed to evaluate the neurological function of rats. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and Nissl staining were respectively employed to determine the infarct condition and neuronal injury of the brain. Iba1 immunohistochemistry was used to show the activation of microglia. Moreover, the synaptic damage and inflammatory level were detected by Western blot. ResultsGJ-4 could significantly improve memory impairment, cerebral infraction, as well as neurological deficits of VD rats induced by MCAO/R. Further research indicated VD-induced neuronal injury was alleviated by GJ-4. In addition, GJ-4 could protect synapse of VD rats by upregulating synaptophysin (SYP) expression, post synaptic density 95 protein (PSD95) expression, and downregulating N-Methyl-D-Aspartate receptor 1 (NMDAR1) expression. Subsequent investigation of the underlying mechanisms identified that GJ-4 could suppress neuroinflammatory responses, supported by inhibited activation of microglia and reduced expression of inflammatory proteins, which ultimately exerted neuroprotective effects on VD. Further mechanistic study indicated that janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) pathway was inhibited by GJ-4 treatment. ConclusionThese results suggested that GJ-4 might serve as a potential drug to improve VD. In addition, our study indicated that inhibition of neuroinflammation might be a promising target to treat VD.

The active ingredients in the anti‐obesity drug bofutsushosan in high‐fat‐diet‐fed obese mice

ABSTRACTAimCombined effects on the body weights and white adipose tissues in high‐fat‐diet‐fed obese mice due to bofutsushosan (BTS) were investigated.MethodsMale ICR mice (four weeks old) were fed a 60% kcal fat diet for five weeks and fed the same diet with administration of aqueous extracts (2.0 g/kg/day) of BTS, component‐removed BTS, and a mixture of the ingredients and the component‐removed BTS for 28 days.ResultsThe BTS extract reduced the body weight from 2 to 28 days after administration while also reducing the weight of the subcutaneous and visceral white adipose tissues after administration for 28 days. Extracts of BTS with Glycyrrhizae radix (Glycyrrhiza root; abbreviated as glycyrrhiza) removed, Rhei rhizoma (rhubarb rhizome; rhubarb) removed, Gardeniae fructus (Gardenia fruit; gardenia) removed, Ephedrae herba (Ephedra herb; ephedra) removed, or Sal mirabilis (sodium sulfate hydrate; mirabilite) removed reduced the anti‐obesity and fat‐loss activity compared to that of the BTS extract after administration for 28 days. Glycyrrhizic acid (0.89% [w/w]) and 0.046%(w/w) sennoside AB calcium salt ameliorated the anti‐obesity activity of BTS with glycyrrhiza removed and rhubarb removed eight days after administration, respectively. Geniposide (0.78% [w/w]) and 0.16% (w/w) ephedrine hydrochloride ameliorated the anti‐obesity and fat‐loss activity of BTS with gardenia removed and with ephedra removed respectively after administration for 28 days.ConclusionGlycyrrhiza, rhubarb, gardenia, ephedra and mirabilite were the active components responsible for the effect of BTS. Glycyrrhizic acid and sennoside AB induced the early phase while geniposide and ephedrine hydrochloride induced the later phase of the anti‐obesity activity of BTS.

Carvacrol methyl ether, a compound from the essential oil of Gardenia jasminoides fruits, exhibits antioxidant effects in the deep-frying of Chinese Youmotou using sunflower oil

Deep-frying using sunflower oil (SFO) requires natural antioxidants, and the preparation of flavored SFO using spices and herbs offers an important method. In the present study, in the deep-frying procedure of Chinese Youmotou at 180 °C, improvements in the levels of total polar compounds (TPC), thiobarbituric acid (TBA), conjugated dienes, conjugated trienes, polymer, viscosity and b* of SFO samples at the 30th hour were significantly inhibited by 50.2%, 43.0%, 62.6%, 37.8%, 61.9%, 24.0% and 50.4% (p < 0.01 or p < 0.05), respectively, after the addition of Fructus gardenia (Gardenia jasminoides fruits, FGEO) essential oil at 0.12 g/kg compared with those in the no-added SFO samples (control samples). Meanwhile, the levels of L* was significantly reduced by 24.1% (p < 0.05). The sensory attributes of the fried product, Chinese Youmotou, including flavor, taste, crispness and overall acceptability, were prominently increased by 37.3%, 32.1%, 62.2% and 53.3% (p < 0.01 or p < 0.05), respectively. Moreover, improvements in the oxidative stability of SFO due to FGEO were attributed to one of its chemical constituents, carvacrol methyl ether. Consequently, SFO flavored by Fructus gardenia could be employed as a flavored vegetable oil for deep-frying procedures.

The Protective Effects of Gardenia jasminoides (Fructus Gardenia) on Amyloid-β-Induced Mouse Cognitive Impairment and Neurotoxicity.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. Although the exact causes of AD have not yet been fully elucidated, cholinergic dysfunction, mitochondrial damage, oxidative stress and neuroinflammation have been recognized as influential factors. Current drugs that are designed to address only a single target are unable to mitigate or prevent the progression of this complicated disease, so new disease-modifying drugs are urgently needed. Chinese herbs with thousand years of effective usage might be a good source for potential drugs. Gardenia jasminoides J. Ellis (Fructus Gardenia) is a common traditional Chinese medicine with tranquilizing effects, which is an important component of widely-used traditional Chinese medicine for dementia. GJ-4 is crocin richments extracted from Gardenia jasminoides J. Ellis. In our study, we attempted to observe the effects of GJ-4 on learning and memory injury induced by amyloid-[Formula: see text] 25-35 (A[Formula: see text] injection in mice. Treatment with GJ-4 dose-dependently enhanced the memory and cognition ability of A[Formula: see text]-injected mice. Preliminary mechanistic studies revealed the protective effect of GJ-4 was related to its protection of neurons and cholinergic dysfunction. The mechanistic results also indicated that GJ-4 could enhance antioxidant capacity and attenuate neuroinflammation. Our results implied that GJ-4 might be a promising drug to improve cognitive and memory impairment, with multiple targets.

Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation

Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage.

Learning and memory improvement and neuroprotection of Gardenia jasminoides (Fructus gardenia) extract on ischemic brain injury rats

Ethnopharmacological relevanceGardenia jasminoides Ellis is a traditional Chinese medicine (TCM) that containing a variety of effective active ingredients and exhibits diverse pharmacological functions, such as anti-inflammatory, antioxidant and nerve protection. Aim of the studyThis study investigated the effect of Gardenia jasminoides extract (GJE) and Geniposide on learning and memory improvement and neuroprotection in a rat model with chronic cerebral ischemia, as well as explore the underlying mechanisms. Materials and methodsThe crude GJE was prepared using the methods of water extraction and alcohol precipitation, and refined by macroporous adsorption resin. The chronic cerebral ischemia model was simulated by permanent occlusion of bilateral common carotid arteries in rats. GJE was taken at three doses groups (150mg/kg, 100mg/kg, 50mg/kg), Geniposide group (50mg/kg), and oral administration for 30 days. Memory function was assessed using Morris water maze test. The morphological changes of hippocampus and related parts of brain in rats by Hematoxylin and Eosin (HE) staining were observed. Moreover, the levels of Acetylcholin Esterase (AchE), Nitric Oxide Synthase (NOS), Malondialdehyde (MDA), Superoxide Dismutase (SOD) in the brain tissue were quantified. ResultsGJE contained 27% gardenoside and 72% total iridoid glycoside. The chronic cerebral ischemia rat model has been proved successfully. The memory function of the rats assessed using Morris water maze test showed that GJE significantly shortened the escape latency of rats, but had no significant improvement on the number of times crossing the platform and the percentage of time spent in the target quadrant. HE staining showed that the apoptosis and necrosis of the cortex and hippocampus in the GJE group were significantly reduced. In addition, it was found that GJE could significantly improved the content of SOD, inhibited NOS and AchE activity in brain tissue, but did not show a significant reduction in the content of MDA. The effect of medium dosage of GJE was the best among these three dose groups and also better than Geniposide according to the results of all the detection index. ConclusionsGJE had the functions of learning and memory improvement and the neuroprotection on chronic cerebral ischemia model rats. The mechanisms were found to be strongly correlated with antioxygen free radical, reduction of NO toxicity and AChE activity, and brain neuron protective effect. GJE could be able to play a better effect on improving chronic cerebral ischemia than Geniposide.

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Genipin is a major active component of Fructus Gardenia, which has been widely used in Traditional Chinese Medicine for the treatment of various cardiovascular diseases. The aim of this study was to investigate the potential effects of genipin on hypertension and the related nephropathy and elucidate the underlying mechanisms of action. We first examined the effects of genipin on blood pressure and renal functions in the Spontaneously Hypertensive (SHR) rats. In the subsequent experiments with human mesangial cells (HMCs), the effects of genipin on angiotensin II (Ang II)-induced HMC proliferation, reactive oxygen species (ROS) generation, and cytokine prodution were examined using the MTT method, 2′,7′-dichlorohydrofluorescein (DCFH-DA) staining, and the corresponding enzyme-linked immunosorbent assay (ELISA) kits, respectively. The effects of genipin on Ang II-induced activation of the MAPK pathway and up-regulation of TLR2, TLR4, and MyD88 were detected by real-time PCR and Western blot and further validated in MyD88 siRNA-transfected HMCs. Genipin not only significantly lowered blood pressure in SHR rats after an 8-week treatment, but effectively improved renal functions, evidenced by decreased serum creatinine and blood urea nitrogen (BUN), as well as urinary microalbumin (m-ALB) and N-acetyl-beta-d-glucosaminidase (NAG) upon administration with genipin. Mechanistic studies conducted in Ang II-treated HMCs showed that genipin was able to counteract Ang II-induced cell proliferation, ROS generation, and pro-inflammatory responses. These effects may be mediated through the TLR/MyD88/MAPK signaling pathway. These findings provide new insights into the molecular mechanisms of genipin in the treatment of renal damage in hypertension, which merits a further investigation.

Effects of Huanglian-Jie-Du-Tang and Its Modified Formula on the Modulation of Amyloid-β Precursor Protein Processing in Alzheimer's Disease Models

Huanglian-Jie-Du-Tang (HLJDT) is a famous traditional Chinese herbal formula that has been widely used clinically to treat cerebral ischemia. Recently, we found that berberine, a major alkaloid compound in HLJDT, reduced amyloid-β (Aβ) accumulation in an Alzheimer’s disease (AD) mouse model. In this study, we compared the effects of HLJDT, four single component herbs of HLJDT (Rhizoma coptidis (RC), Radix scutellariae (RS), Cortex phellodendri (CP) and Fructus gardenia (FG)) and the modified formula of HLJDT (HLJDT-M, which is free of RS) on the regulatory processing of amyloid-β precursor protein (APP) in an in vitro model of AD. Here we show that treatment with HLJDT-M and its components RC, CP, and the main compound berberine on N2a mouse neuroblastoma cells stably expressing human APP with the Swedish mutation (N2a-SwedAPP) significantly decreased the levels of full-length APP, phosphorylated APP at threonine 668, C-terminal fragments of APP, soluble APP (sAPP)-α and sAPPβ-Swedish and reduced the generation of Aβ peptide in the cell lysates of N2a-SwedAPP. HLJDT-M showed more significant APP- and Aβ- reducing effects than berberine, RC or CP treatment alone. In contrast, HLJDT, its component RS and the main active compound of RS, baicalein, strongly increased the levels of all the metabolic products of APP in the cell lysates. The extract from FG, however, did not influence APP modulation. Interestingly, regular treatment of TgCRND8 APP transgenic mice with baicalein exacerbated the amyloid plaque burden, APP metabolism and Aβ production. Taken together, these data provide convincing evidence that HLJDT and baicalein treatment can increase the amyloidogenic metabolism of APP which is at least partly responsible for the baicalein-mediated Aβ plaque increase in the brains of TgCRND8 mice. On the other hand, HLJDT-M significantly decreased all the APP metabolic products including Aβ. Further study of HLJDT-M for therapeutic use in treating AD is warranted.

Fructus Gardenia Extract Ameliorates Oxonate-Induced Hyperuricemia with Renal Dysfunction in Mice by Regulating Organic Ion Transporters and mOIT3

The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE) have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered to hyperuricemic and normal mice for 1 week. Serum and urinary levels of uric acid, creatinine and blood urea nitrogen (BUN), and fractional excretion of uric acid (FEUA) were measured. The mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), ATP-binding cassette, subfamily G, 2 (mABCG2), organic anion transporter 1 (mOAT1), mOAT3, oncoprotein induced transcript 3 (mOIT3), organic cation/carnitine transporters in the kidney were analyzed. Simultaneously, Tamm-Horsfall glycoprotein (THP) levels in urine and kidney were detected. FGE significantly reduced serum urate levels and increased urinary urate levels and FEUA in hyperuricemic mice. It could also effectively reverse oxonate-induced alterations in renal mURAT1, mGLUT9, mOAT1 and mOIT3 expressions, as well as THP levels, resulting in the enhancement of renal uric acid excretion. Moreover, FGE decreased serum creatinine and BUN levels, and up-regulated expression of organic cation/carnitine transporters, improving renal dysfunction in this model. Furthermore, FGE decreased renal mABCG2 expressions in hyperuricemic mice, contributing to its beneficial actions. However, further investigation is needed in clinical trials of FGE and its bioactive components.

Orthogonal Test Design for Optimization of the Extraction of Flavonid from the Fructus Gardeniae

ObjectiveIt is imperative to provide some consistent experimental results for the extraction of flavonid from Fructus Gardeniae. MethodsThe key extraction parameters that influenced the yield of flavonid from Fructus Gardeniae were optimized by employing an orthogonal experiment [L9(3)4], including the ratio of buffer solution (Na2B4O7·10H2O) to raw material, concentration of Fructus Gardeniae in extracting solution, extraction time and pH of buffer solution. An UV/Vis detector was used to perform the qualitative and quantitative analyses of the extracted flavonid with the using of the standard sample. ResultsThe maximum extraction yield of the crude extract was 5.0533 (mg/g) after 20 min when the mass ratio of Na2B4O7·10H2O to raw material was 0.4%, the concentration of Fructus Gardeniae in the extraction solution was 1/12 (g/mL), and pH of buffer solution was 4.5. The positive reactions to the Molish and HCl-Mg tests suggested that the extracted compound was flavonoid, and FTIR measurements also identified the presence of flavonoid in the extracts. ConclusionThis work is expected to provide a basis for further research, development, and utilization of Fructus gardenia in flavonid extraction.

P03-366 - An epidemiological study of concomitant use of herbal medicine and antipsychotics in schizophrenic patients: implication for herb-drug interaction

Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. A total of 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%–38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80–4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06–4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. Our study suggests that concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

An Epidemiological Study of Concomitant Use of Chinese Medicine and Antipsychotics in Schizophrenic Patients: Implication for Herb-Drug Interaction

BackgroundHerb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia.Methods and FindingsIn this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%–38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80–4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06–4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes.ConclusionsConcomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

Active ingredients of traditional Japanese (kampo) medicine, inchinkoto, in murine concanavalin A-induced hepatitis

Aim of the study The traditional Japanese (kampo) medicine inchinkoto (ICKT) is used in Eastern Asia as a choleretic and hepatoprotective agent. Previously, we reported that ICKT ameliorates murine concanavalin A (con A)-induced hepatitis via suppression of interferon (IFN)-γ and interleukin (IL)-12 production. In the present study, we investigated the active ingredients of ICKT. Materials and methods ICKT and extracts of its component herbs were fractionated, and their effects on liver injury and cytokine production in vivo (biochemical markers of liver injury and cytokine levels in serum) and in vitro (cytokine and nitrite production in the cultures of splenocytes and peritoneal macrophages). Results Decoctions of component herbs, Artemisiae Capillari Spica (Artemisia capillaris Thunberg: ‘Inchinko’ in Japanese), Gardeniae Fructus (Gardenia jasminoides Ellis: ‘Sanshishi’) and Rhei Rhizoma (Rheum palmatum Linné: ‘Daio’) were administered orally. Inchinko and Sanshishi decreased serum transaminases and IFN-γ concentrations. Examination of fractions of component herbs suggested that capillarisin, a component of Inchinko, has potent hepatoprotective activity in vivo. In in vitro studies, capillarisin and genipin, an intestinal metabolite of geniposide that is contained in Sanshishi, were examined. IFN-γ production was significantly suppressed by capillarisin and genipin in con A-stimulated splenocyte culture. Genipin also suppressed IL-1β, IL-6, and IL-12p70 synthesis. Capillarisin and genipin decreased nitrite release from IFN-γ-stimulated macrophages. Conclusions These results suggested that both Inchinko and Sanshishi may contribute to the protective effects of ICKT against con A hepatitis. Capillarisin was found to be potently hepatoprotective, and genipin may also contribute, especially via modulation of cytokine production.

Direct process integration of extraction and expanded bed adsorption in the recovery of crocetin derivatives from Fructus Gardenia

A process that integrated an extraction tank (EXT) and an expanded bed adsorption (EBA) into a new system EXT-EBA for direct purifying crocetin derivatives from Fructus Gardenia was described. Conditions were set to allow the extraction and purification in a single step. A comparison between the integrated process and the conventional process to purify crocetin derivatives was presented. The integrated process resulted in 52.79% recovery of crocin compared to 24.12% in the conventional process. The process time and solvent used were decreased in the integrated process. The result suggests that the EXT-EBA integrates extraction, clarification, and purification in a single step, greatly simplifying the process flow and reducing the cost and time of extraction and purification of crocetin derivatives from Fructus Gardenia.