Gut Microbiome and Metabolomics Study of Selenium-Enriched Kiwifruit Regulating Hyperlipidemia in Mice Induced by a High-Fat Diet.

Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as Parabacteroides, Bacteroides, and Allobaculum in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the Ada, Gda, Pank1, Ppara, Pparg, and Cd36 genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.

SAR-guided development of indole-matrine hybrids as potential anticancer agents via mitochondrial stress/cytochrome c/caspase 3 signaling pathway.

Matrine is a clinically used adjuvant anticancer drug, yet its mild potency limited its application. To improve the anticancer activity of matrine, a total of 31 indole-matrine hybrids were constructed in four rounds of SAR-guided iterative structural optimization process. All of the synthesized compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines (Hela, MCF-7, SGC-7901, HepG2) and two normal cell lines (GES-1, LO2). The most active hybrid 8g exhibited the anticancer IC50 values of 0.9 to 1.2 µM, which was 3-magnitude of orders more potent than matrine. 8g also showed better selectivity towards cancer cells with the selectivity index value raised from 1.5 to 6.2. Mechanistic studies demonstrated a mitochondrial distribution for 8g by intracellular click chemistry approaches, which led to the discovery that 8g strongly induced mitochondrial stress, as evidenced by impaired energy metabolism, depolarized mitochondrial membrane potential, overload of mitochondrial calcium and escalated ROS production. 8g-induced mitochondrial stress further led to the release of cytochrome c and subsequent activation of caspase 3, which significantly promoted cellular death and inhibited colony formation.

Prevalence and risk factors of belching disorders: A cross-sectional study among freshman college students.

OBJECTIVES: Belching disorders seriously affect quality of life; however, their prevalences and risk factors remain unknown. The aim of our study was to determine the prevalence and risk factors, particularly lifestyle factors, of belching disorders among freshman college students in central China. METHODS: A cross-sectional study was conducted in September 2019 in Huazhong University of Science and Technology (Wuhan, Hubei Province, China). The subjects were asked to complete a self-administered questionnaire for data collection, including sociodemographic information, lifestyle factors, and gastrointestinal symptoms. Belching disorder was diagnosed based on the Rome IV criteria. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for belching disorders. RESULTS: A total of 3335 subjects were enrolled, and 78.26% were men. Among them, 1.95% (65/3335) reported belching disorders. Significant differences in the Pittsburgh Sleep Quality Index (PSQI), Student-Life Stress Inventory (SLSI) scores, and consumption of whole grains, black tea, coffee were found between the belching and non-belching groups. Multivariate logistic regression analysis showed that coffee consumption at least once weekly and a high total SLSI score (over mean + standard deviation) were independent risk factors for belching disorders, while intake of whole grains at least once weekly was a protective factor. CONCLUSIONS: Excessive belching is a common disorder among freshman college students in central China. Lifestyle factors, including consumption of whole grains and coffee, and stress, were associated with belching disorders. Therefore, dietary intervention may be a potential management for belching disorders.

Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant A549/DDP Cells via the AKT-mTOR-c-Myc Signaling Pathway.

Tumor cells, especially drug-resistant cells, predominately support growth by glycolysis even under the condition of adequate oxygen, which is known as the Warburg effect. Glucose metabolism reprogramming is one of the main factors causing tumor resistance. Previous studies on Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of tumors in combination with chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with cisplatin on cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that cisplatin-resistant A549/DDP cells exhibited increased glucose consumption, lactate production, and expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M1/2 (PKM1/2), pyruvate kinase M2 (PKM2), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA), compared with cisplatin-sensitive A549 cells. SMI combined with cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic enzymes, such as HK2, PKM1/2, GLUT1, and pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p-Akt, p-mTOR, and c-Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of cisplatin via glucose metabolism reprogramming. Therefore, the combination of SMI and cisplatin may be a potential therapeutic strategy to treat cisplatin-resistant nonsmall cell lung cancer.

Comprehensive identification of potential antioxidant components in the aerial parts of Polygonum chinense L. var. hispidum using ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

The aerial parts of Polygonum chinense L. var. hispidum are one of the key herbs in Cantonese herbal tea, which is quite a common local beverage in LingNan area of China. Previous investigation has found that this herb possesses antioxidant activity and the ethyl acetate fraction of its ethanol extract shows the strongest antioxidant activity. However, little is known about its antioxidant chemical constituents. The aim of this research was to investigate the active constituents of this plant by identifying and characterizing the chemical profile in ethyl acetate fraction using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry, which can provide characteristic ultraviolet absorption, accurate molecular weight, and diagnostic tandem mass spectrometry fragment ions. As a result, 85 compounds were identified including 22 flavonoids, 12 ellagic acids, 34 ellagitannins, 16 phenolic acids, and one phenolic amide. All the phenolic compounds identified in this work, especially ethyl gallate, geraniin, chebulagic acid, and quercitrin with the higher peak areas in the ultra high performance liquid chromatography with mass spectrometry chemical profile of this plant, could be the bioactive principles responsible for the antioxidant activity. These findings in the present study could benefit further studies involving the functions and chemicals of this plant, and provide scientific evidence for usage of Cantonese herbal tea.

Therapeutic effects of hirsutella sinensis on the disease onset and progression of amyotrophic lateral sclerosis in SOD1G93A transgenic mouse model.

AIMS: Although the pathophysiology of amyotrophic lateral sclerosis (ALS) is still not completely understood, the deregulated microglia polarization and neuroinflammation have been shown to contribute to the pathogenesis and progression of this disease. In the present study, we aimed to determine whether hirsutella sinensis (HS) could reduce neuroinflammatory and pathological changes in the spinal cord of SOD1G93A model mice of ALS and consequently ameliorate disease onset and progression. METHODS: SOD1G93A mice were chronically treated with HS by gavage. Their lifespan was recorded, and motor behavior was evaluated by rotarod test. The pathological changes in skeletal muscles and motor neurons in spinal cords were assessed by immunofluorescent staining and hematoxylin-eosin staining. The microglia activation and neuroinflammation were determined by immunofluorescent staining and RT-PCR. RESULTS: Our data suggested that repeated HS administration prolonged the lifespan and extended disease duration of ALS mice without significant delay on disease onset. HS ameliorated the pathological changes in the motor neurons and gastrocnemius muscles. Moreover, HS promoted the transition of microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype in the spinal cord of ALS mice. CONCLUSION: All these findings indicate that HS may serve as a potential therapeutic candidate for the treatment of ALS.

Neuroprotective Effect of Cyperi rhizome against Corticosterone-Induced PC12 Cell Injury via Suppression of Ca2+ Overloading.

Cyperi Rhizoma (CR) is a well-known functional food and traditional herbal medicine in Asian countries for the treatment of menstrual or emotional disturbances in women. Recent studies have shown the pharmacological effects of CR on neuronal diseases, such as Parkinson's disease (PD) and depression. Thus, the neuroprotective effect of CR might play a vital role in exerting its effect. Here, corticosterone-induced PC12 cells were applied to screen the active fraction of CR and evaluate its neuroprotective effect. The results indicated that the fraction containing medium-polarity chemical constituents (CR-50E) displayed the best protection effect. CR-50E could increase the cell viability and reduce cell apoptosis through inhibiting oxidative stress and decreasing the lactate dehydrogenase LDH release induced by corticosterone. Further, the mechanism of action was explored by cell metabolomics. The result showed CR-50E mediated the sphingolipids metabolism of corticosterone-induced PC12 cells, which suggested inhibition of Ca2+ overloading may involve the protection of CR-50E against cell damage. The expression levels of three key proteins in calcium transport, including phospholipase A2 (PLA2), calcium/calmodulin independent protein kinase II (CaMK II), and caspase-3, confirmed the above result by Western blot. The findings suggest that CR-50E can suppress the disequilibrium of calcium homeostasis-mediated apoptosis by improving the abnormal sphingolipids metabolism as well as remedying the damage of the cell membrane.

Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways.

BACKGROUND: Qingjie Fuzheng granules (QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer (CRC). However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs' anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways. AIM: To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8. METHOD: First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase (LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21, Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3K/AKT and ERK signaling pathways was examined using the western blot assay to investigate the possible mechanism. RESULTS: MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by (6.90% ± 1.03%)-(59.70% ± 1.51%) (HCT-116; P < 0.05) and (5.56% ± 4.52%)-(49.44% ± 2.47%) (HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002 (HCT-116; P < 0.01) and from 0.56 ± 0.054 to 0.81 ± 0.044 (HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells. QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3K, AKT and ERK. CONCLUSION: These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3K/AKT and ERK signaling pathways.

Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome.

AIM: To observe whether there are differences in the effects of electro-acupuncture (EA) and moxibustion (Mox) in rats with visceral hypersensitivity. METHODS: EA at 1 mA and 3 mA and Mox at 43 °C and 46 °C were applied to the Shangjuxu (ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells (MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine 3 receptor (5-HT3R) and 5-HT4R expressions in the colons were measured. RESULTS: Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 mA and 3 mA groups (1 mA: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 mA: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43 °C and 46 °C groups (43 °C: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46 °C: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3R and 5-HT4R in the colon of Mox 46 °C group were decreased compared with model group (MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION: The analgesic effects of Mox at 46 °C are greater than those of Mox at 43 °C, EA 1 mA and EA 3 mA.

Comparison of Electroacupuncture and Moxibustion for Relieving Visceral Hypersensitivity in Rats with Constipation-Predominant Irritable Bowel Syndrome.

Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS). Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon. Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (P all < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (P all < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (P all < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (P all < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (P both < 0.01). Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox.

[Effect of Electroacupuncture and Moxibustion on Visceral Pain and Expression of VR 1 and HSP 70 of "Tianshu" (ST 25) Region in Colorectal Distension-induced Visceral Hypersensitivity Rats].

OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion (Moxi) on visceral pain and expression of vanilloid receptor subtype 1 (VR 1) and heat shock protein (HSP)70 in "Tianshu" (ST 25) region in colorectal distension (CRD)-induced visceral hypersensitivity (VHS) rats. METHODS: Fifty male SD rats were randomly divided into normal control, VHS model, 43℃-moxi, 46℃-moxi, 1 mA-EA and 3 mA-EA groups (n=10 in each group). The VSH model was established by CRD once daily for 14 days. EA or Moxi stimulation was applied to bilateral "Tianshu" (ST 25) for 10 min, once daily for consecutive 10 days. The abdominal withdrawal reflex (AWR) scores (0-4 points) were rated according to Al-Chaer's and coworkers' standards (2000) and the expression levels of VR 1 and HSP 70 in bilateral ST 25 area tissues detected by immunohistochemistry. RESULTS: The AWR scores for 20, 40, 60 and 80 mmHg CRD pressures were significantly increased compared to the normal control group (P<0.01) and notably decreased after 43℃- and 46℃-moxi, and 1 mA- and 3 mA-EA stimulation of bila-teral ST 25 in comparison with the model group (P<0.05, P<0.01), and the effect of 46℃-moxi was apparently superior to those of 1 mA-EA at 40 and 80 mmHg, and 3 mA-EA at 40 mmHg (P<0.05). After modeling, the expression of both VR 1 and HSP 70 (percentages of area of positive-cells) in ST 25 region had no significant changes (P>0.05). Compared to the model group, the expression levels of VR 1 in the 43℃-moxi and 46℃-moxi groups, and HSP 70 in the 43℃-moxi and 46℃-moxi, 1 mA-EA and 3 mA-EA groups were significantly up-regulated (P<0.01), but without obvious changes in the expression of VR 1 in the 1 mA-EA and 3 mA-EA groups (P>0.05). The effects of 46℃-moxi were considerably better than those of 43℃-moxi, 1 mA-EA and 3 mA-EA in up-regulating VR 1 and HSP 70 expression (P<0.05, P<0.01). No significant differences were found among the 43℃-moxi, 1 mA-EA and 3 mA-EA groups in the expression of VR 1 and HSP 70 (P>0.05). CONCLUSIONS: Moxibustion at 43℃ and 46℃ and EA at 1 mA and 3 mA, especially the 46℃-moxi, can relieve visceral pain in visceral hypersensitivity rats, which may be related to their effects in up-regulating expression of VR 1 and HSP 70 in "Tianshu" (ST 25) area.

Effects of daidzein in regards to cytotoxicity in vitro, apoptosis, reactive oxygen species level, cell cycle arrest and the expression of caspase and Bcl-2 family proteins.

In the present study, the in vitro cytotoxicity of daidzein was evaluated in human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. BEL-7402 cells were sensitive to daidzein treatment, with an IC50 value of 59.7±8.1 µM. Daidzein showed no cytotoxic activity toward A549, HeLa, HepG-2 and MG-63 cells. Daidzein increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Morphological and comet assays showed that daidzein effectively induced apoptosis in BEL-7402 cells. Additionally, daidzein caused cell cycle arrest at the G2/M phase in the BEL-7402 cell line. Daidzein downregulated the expression of Bcl-2, Bcl-x and Baid proteins and upregulated the levels of Bim protein in the BEL-7402 cells. The results demonstrated that daidzein induced BEL-7402 cell apoptosis through an ROS-mediated mitochondrial dysfunction pathway.

Moxibustion combined with acupuncture increases tight junction protein expression in Crohn's disease patients.

AIM: To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction (TJ) proteins. METHODS: Sixty patients diagnosed with mild to moderate Crohn's disease (CD) were allocated into the herb-partitioned moxibustion combined with acupuncture (HMA) group (n = 30) or the mesalazine (MESA) group (n = 30) using a parallel control method. There were 2 sets of acupoints used alternately for HMA treatment. The following points were included in Set A: ST25 (Tianshu), RN6 (Qihai), and RN9 (Shuifen) for herb-partitioned moxibustion and ST36 (Zusanli), ST37 (Shangjuxu), LI11 (Quchi), and LI4 (Hegu) for acupuncture. The points for Set B included BL23 (Shenshu) and BL25 (Dachangshu) for herb-partitioned moxibustion and EX-B2 of T6-T1 (Jiajixue) for acupuncture. The patients received the same treatment 6 times a week for 12 consecutive weeks. The MESA group received 1 g of mesalazine enteric coated tablets 4 times daily for 12 consecutive weeks. Intestinal tissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session. Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1 (ZO-1), occludin, and claudin-1. The mRNA levels were also evaluated. RESULTS: After the treatment, both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients; the patients treated with HMA showed better improvement. HMA significantly increased the expression of ZO-1 (P = 0.000), occludin (P = 0.021), and claudin-1 (P = 0.016). MESA significantly increased the expression of ZO-1 (P = 0.016) and occludin (P = 0.026). However, there was no significant increase in the expression of claudin-1 (P = 0.935). There was no statistically significant difference between the two groups for the expression of occludin and claudin-1 (P > 0.05). The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group (2333.34 ± 352.51 vs 2160.38 ± 307.08, P = 0.047). HMA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.017), and claudin-1 mRNA (P = 0.017). MESA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.042), and claudin-1 mRNA (P = 0.041). There was no statistically significant difference between the two groups in the expression of occludin and claudin-1 mRNA (P > 0.05). However, the HMA group showed a significant improvement in ZO-1 mRNA expression compared with the MESA group (2378.17 ± 308.77 vs 2200.56 ± 281.88, P = 0.023). CONCLUSION: HMA can repair intestinal epithelial barrier lesions and relieve inflammation by upregulating the expression of TJ proteins and their mRNAs.

Biomimetic synthesis: discovery of xanthanolide dimers.

Starting from xanthatin, the biomimetic synthesis of 4ß,5ß-epoxyxanthatin-1α,4α-endoperoxide, a novel monomeric xanthanolide, has been achieved. Moreover, four unprecedented xanthanolide dimers were synthesized by three different dimerizations of xanthatin, either in a head-to-head or head-to-tail fashion. Notably, these dimeric compounds were firstly identified as artifacts in the laboratory, and two of them, mogolides A and B, proved to be natural products present in the Xanthium mogolium Kitag plant.

Enantioselective and collective syntheses of xanthanolides involving a controllable dyotropic rearrangement of cis-ß-lactones.

Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-ß-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products.

Bama miniature pigs (Sus scrofa domestica) as a model for drug evaluation for humans: comparison of in vitro metabolism and in vivo pharmacokinetics of lovastatin.

The objective of this study was to demonstrate that Bama miniature pigs are a suitable experimental animal model for the evaluation of drugs for man. To this end, in vitro lovastatin metabolism at the minipig liver microsomal level and in vivo pharmacokinetics were studied. Results were compared with those obtained from humans. Our data indicate that the main metabolites and enzyme kinetic parameters of lovastatin metabolism are similar in pigs and humans. Triacetyloleandomycin, a specific inhibitor of human CYP3A4, inhibited the metabolism of lovastatin in pig and human liver microsomes. In addition, the pharmacokinetic parameters and absolute bioavailability suggested that the absorption and elimination of lovastatin in Bama miniature pigs were similar to those in humans. Lovastatin was distributed across many organs in pigs, but the highest levels were found in the stomach, intestines, and liver. Within 96 h, 7% and 82% of the given dose was excreted in the urine and feces, respectively. In addition, no significant species differences in the plasma protein binding ratio of lovastatin and the rates of lovastatin hydrolysis to beta-hydroxyacid lovastatin were apparent. From these results, we conclude that Bama miniature pigs are suitable for use in drug evaluation studies.