Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine.

Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

IFN-γ differential expression in the hypothalamus-pituitary-ovary axis of thyroidectomized rats.

IFN-γ is critical for both thyroid and ovarian function, while thyroxine, secreted from the thyroid gland, regulates the ovarian function via the hypothalamus-pituitary -ovary axis. However, the effect of thyroxine on INF-γ involved in the regulation of hypothalamic pituitary ovarian axis ovarian function is hitherto unknown. Therefore, we set up three groups including a sham-operated group, an experimental thyroidectomized group, and an experimental thyroidectomized group treated with T4 to reveal the IFN-γ expression levels in the in the hypothalamus, pituitary gland, and ovary by immunohistochemical staining, RT-PCR, and Western blotting. IFN-γ-like immunoreactive-positive substances were visualized in the hypothalamus, pituitary gland, and ovary, which were located mainly in the cytoplasm of the hypothalamic neurons anterior pituitary cells, luteal cells, and theca cells in the ovary of hypothyroidism rats, respectively. RT-PCR and Western blotting showed that the rats in the experimental thyroidectomized group treated with T4 had significantly elevated expression of IFN-γ at both the mRNA and protein levels. Thyroxine affects the expression of IFN-γ in the thalamus-pituitary-ovarian axis, which may influence the secretion of IFN-γ to regulate ovarian function during hypothyroidism. This work highlights the potential effect of thyroxine on the involvement of INF-γ in the modulation of the ovarian function in the hypothalamic-pituitary-ovarian axis.

Efficacy of Ginkgo biloba Extract Combined with Hormones in the Treatment of Sudden Deafness and Its Effect on the Reactivity of Peripheral Blood T Cell Subsets.

This work was aimed at exploring the efficacy of Ginkgo biloba extract combined with hormones in the treatment of sudden deafness and the influence on the reactivity of peripheral blood T cell subsets (PBTCSs). In this work, 64 patients with sudden deafness who were treated in The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2019 to August 2022 were selected as the research objects. The patients were randomly divided into a hormone group (treatment with prednisone acetate, n = 34) and a combination group (treatment with Ginkgo-Damole combined with prednisone acetate, n = 30). After the two groups of patients were treated in different ways, their efficacy, symptom improvement, changes in blood rheology, and PBTCSs were compared. The total effective rates (TERs) of the hormone group and the combination group were 76.32% and 95.73%, respectively (P < 0.05). The fibrinogen contents of the patients in the combination group were obviously lower than those in the hormone group after 5 d, 7 d, and 10 d of treatment (P < 0.05). The high blood viscosity (HBV) values of patients in the combination group at 5 d, 7 d, and 10 d after treatment were greatly lower than those in the hormone group (P < 0.05). The low blood viscosity (LBV) values after 3 d, 7 d, and 10 d of treatment in the combined group were much lower in contrast to those in the hormone group (P < 0.05). The CD3+, CD4+, and CD4+/CD8+ in peripheral blood in the combination group were sharply higher while the CD8+ in the combined group was lower in contrast to the hormone group (P < 0.05). There was no visible difference in the incidence of adverse reactions between the two groups of patients after treatment (P > 0.05). In conclusion, the combined application of Ginkgo biloba extract and hormones could effectively improve the abnormal hemorheological indexes of patients with sudden deafness and effectively relieve the imbalance of PBTCSs, which was safe.

Traditional Chinese medicine suppressed cancer progression by targeting endoplasmic reticulum stress responses: A review.

Cancer has a high morbidity and mortality; therefore, it poses a major global health concern. Imbalance in endoplasmic reticulum homeostasis can induce endoplasmic reticulum stress (ERS). ERS has been shown to play both tumor-promoting and tumor-suppressive roles in various cancer types by activating a series of adaptive responses to promote tumor cell survival and inducing ERS-related apoptotic pathways to promote tumor cell death, inhibit tumor growth and suppress tumor invasion. Because multiple roles of ERS in tumors continue to be reported, many studies have attempted to target ERS in cancer therapy. The therapeutic effects of traditional Chinese medicine (TCM) treatments on tumors have been widely recognized. TCM treatments can enhance the sensitivity of tumor radiotherapy, delay tumor recurrence and improve patients' quality of life. However, there are relatively few reports exploring the antitumor effects of TCM from the perspective of ERS. This review addresses the progress of TCM intervention in tumors via ERS with a view to providing a new direction for tumor treatment.

Comparison of the Gut Microbiota Between Pulsatilla Decoction and Levofloxacin Hydrochloride Therapy on Escherichia coli Infection.

Gut microbiota serves as a critical indicator for gut health during treatment of pathogenic bacterial infection. Both Pulsatilla Decoction (abbreviated to PD, a traditional Chinese medicine compound) and Levofloxacin Hydrochloride (LVX) were known to have therapeutic effects to intestinal infectious disease. However, the changes of gut microbiota after PD or LVX treatment remain unclear. Herein, this work aimed to investigate the changes of intestinal flora after PD or LVX therapy of Escherichia coli infection in rats. Results revealed that PD exhibited a valid therapeutic approach for E. coli infection via the intestinal protection, as well as the inhibited release of IL-8 and ICAM-1. Besides, PD was beneficial to rebuild the gut microbiota via restoring Bacteroidetes spp in the composition of the gut microbiota. Comparatively, LVX treatment promoted the infection and ravaged gut microbiota by significantly decreasing Bacteroidetes and increasing Firmicutes. These findings not only highlight the mechanism of Chinese herbal formula, but extend the application of PD as veterinary medicine, feed additive and pre-mixing agent for improving the production of animal derived foods.

Synchronous vasomotion of skin microvessels at acupoints on the twelve main meridians of beagle dogs.

BACKGROUND/PURPOSE: Synchronous microvascular vasomotion was detected at acupoints in our previous human study. This present study aimed to characterize the skin microvascular vasomotion at acupoints on the twelve meridians of beagle dogs. MATERIALS AND METHODS: Two acupoints were selected on each meridian and exactly located at the rosy red spots by an electrochemical color-appearing method, where the electrical resistance was measured. The skin blood flow at acupoints was recorded by laser Doppler flowmetry (LDF), and microvascular vasomotion was analyzed according to LDF waveforms. RESULTS: The skin electrical resistance at acupoints was significantly lower than that at control non-acupoints. The LDF waveforms at acupoints were sinusoidal, which showed the synchronization of the microvascular vasomotion. The spectral analysis revealed that the vasomotion frequencies at acupoints on the same meridian were identical but not among different meridians, and the frequencies on the twelve main meridians displayed a constant order. CONCLUSION: The skin microvascular vasomotion is synchronous at acupoints of beagle dogs and has a specific frequency along the meridian, and the electrochemical color-appearing method is a feasible strategy for the precise and visual location of acupoints. The study provides evidence for the universality of synchronous vasomotion of skin microvessels at acupoints.

Anti-inflammatory and antiviral activities of cynanversicoside A and cynanversicoside C isolated from Cynanchun paniculatum in influenza A virus-infected mice pulmonary microvascular endothelial cells.

BACKGROUND: Outbreaks of the influenza A virus (IAV) often occur in various avian and mammalian species, including humans, causing serious respiratory injury worldwide. Therapeutic actions are limited to vaccines and a few antiviral drugs. Combination antiviral compounds and anti-inflammatory modulators to control the propagation of viruses would be more efficient therapeutic strategies for infectious diseases. PURPOSE: This study was designed to isolate anti-inflammatory and antiviral compounds from Cynanchun paniculatum and elucidate their potential molecular mechanisms. METHODS/STUDY DESIGNS: Bioactivity-guided isolation (via in vitro anti-inflammatory assay) was performed on the ethanolic extract of C. paniculatum, the structures of active compounds were elucidated by comparing spectral data (ESI-MS, 1H NMR and 13C NMR) with literature values. The antiviral activity of active compounds against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Inhibitory effects of active compounds on influenza A/FM1/1/47 (H1N1) virus infection were also determined by RT-PCR. Effect of active compounds on NF-kB and MAPK signaling pathways after virus infection was determined by ELISA. RESULTS: Two compounds that showed great anti-inflammatory activity were isolated from C. paniculatum and elucidated as cynanversicoside A and cynanversicoside C. Cytokine assay demonstrated that cynanversicoside A and cynanversicoside C can suppress the production of TNF-α, IL-6 and IL-1ß in Mice Pulmonary Microvascular Endothelial Cells (MPMEC) after Influenza virus A/FM/1/47 infection (p < .05) and also decreased the expressions of p-p65 and p-IκBα in infected cells. Furthermore, the phosphorylation of p38, ERK and JNK was also significantly attenuated. Subsequently, cynanversicoside A and cynanversicoside C treatment resulted in decreased viral replication and viral mRNA synthesis. CONCLUSIONS: These results indicate that cynanversicoside A isolated from C. paniculatum has potent anti-inflammatory and antiviral effects on IAV-infected MPMEC by the regulation of NF-κB and MAPK signaling pathways.

Effects of aqueous extracts of Taraxacum Officinale on expression of tumor necrosis factor-alpha and intracellular adhesion molecule 1 in LPS-stimulated RMMVECs.

BACKGROUND: Mastitis gives rise to big financial burden to farm industry (mainly dairy production) and public health. Its incidence is currently high and therefore, highly effective treatments for therapy, especially with natural products are required. Taraxacum officinale has been reported to use for anti-inflammation. However, its effect on endothelium during mastitis has not been reported. METHODS: We firstly established inflammation experimental model of rat mammary microvascular endothelial cells (RMMVECs). We evaluated the effects of dandelion leaf aqueous extracts (DAE) on LPS-induced production of inflammatory mediators in RMMVECs by enzyme-linked immunosorbent assay and Western blot. We treated RMMVECs with 1 µg/ml LPS for 4 h and then incubated with 10, 100 and 200 µg/mL DAE for 4, 8, 12 and 24 h. The expression (mRNA and protein level) of targets (tumor necrosis factor-alpha (TNF- α) and Intracellular Adhesion Molecule 1 (ICAM1) was analyzed by employing real-time PCR and Western blots. The in vivo anti-inflammatory effect of DAE on mastitis within an Staphylococcus aureus-induced mouse model was also determined. RESULTS: The obtained results showed that dandelion extracts at the concentration of 100 and 200 µg/mL could significantly inhibit both TNF-α and ICAM-1 expression in all time points checked while 10 µg/mL of dandelion only suppress both expression at 8 and 12 h post-treatment. The in vivo tests showed that the DAE inhibited the expression of TNF-α and ICAM-1 in a time-dependent manner. CONCLUSIONS: All results suggest that the endothelium may use as as a possible target of dandelion for anti-inflammation.

[Effect of berberine on nitric oxide release of rat intestinal mucous microvascular endothelial cells].

OBJECTIVE: To study the effect of berberine on the release of nitric oxide (NO) by rat intestinal mucous microvascular endothelial cells (RIMECs) cultured in vitro for exploring the pharmacological mechanism of berberine in treating intestinal disease. METHODS: Cultured RIMECs in vitro were identified adopting immunofluorescent stain with factor VIII-related antigen. NO level in the supernatant of normal cell culture or cell culture treated with different concentrations of berberine was detected with colorimetry at the 3rd, 6th, 9th and 12th h and compared. RESULTS: Compared with that in the normal control group, NO level increased more obviously in the berberine treated groups, and the best effect was shown in the 5 microg/mL berberine treated group. CONCLUSION: One of the important pharmacological mechanisms of berberine might be through promoting the endogenous NO release to induce endothelium-dependent dilatation of microvascular in intestinal mucosa, thus to improve the local microcirculation of intestine.

Effect of anemonin on NO, ET-1 and ICAM-1 production in rat intestinal microvascular endothelial cells.

Anemonin (the dilactone of cyclobutane-1, 2-diol-1, 2-diacrylic acid) was isolated from the root of Pulsatilla chinensis Regel. Pulsatilla chinensis Regel has been used in the treatment of enteritis in China for years. However, only little was known about the mechanism underlying its anti-inflammatory effects. We investigated the effect of anemonin on the release of nitric oxide (NO), endothelin-1 (ET-1) and soluble intercellular adhesion molecule-1 (sICAM-1) induced by lipopolysaccharide (LPS) in primary cultures of rat intestinal microvascular endothelial cells (RIMECs). RIMECs were challenged with 1 microg/ml LPS with or without the presence of various concentrations of anemonin (1, 5 and 10 microg/ml). Anemonin significantly inhibited the production of NO and ET-1 induced by LPS at a concentration of 5 microg/ml and at 10 microg/ml anemonin down-regulated LPS-induced sICAM-1 expression. Anemonin itself had no effect on either factor. These findings suggest that anemonin may exert some beneficial therapeutic action in intestinal inflammation, at least in part by inhibiting the production of NO, ET-1 and ICAM-1 in RIMECs and thus preventing intestinal microvascular dysfunction.

[Effect of electroacupuncture on expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat ].

OBJECTIVE: To observe effect of electroacupuncture at "Zusanli" (ST 36) on expression of interferon-gamma (IFN-gamma)-like immunoreactive substance in spinal cord of the rat and to probe the mechanism. METHODS: The IFN-gamma-like immunoreactive positive cell number in spinal cord of the rat was investigated with immunohistochemical SP method and microscopy. RESULTS: After electroacupuncture at "Zusanli" (ST 36), IFN-gamma-like immunoreactive positive cell number in the spinal cord of the rat with electroacupuncture plus immunosuppression did not significantly change (P > 0.05). The number of positive cells in the dorsal horn in the rats with immunosuppression was significantly less than that in the normal control group (P < 0.05) with no significant change in other parts and with no significant difference between the electroacupuncture group and the control group (P > 0.05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can increase expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat, and acupuncture activates the nerve-immunoregulative network possibly by IFN-gamma as medium.