Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from Angelica sinensis and Its Bioinspired Total Synthesis.

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects.

To provide complementary information and reveal the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multiomics study of hormone receptor-negative (HR-) and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), and mesenchymal stem-like. These 3 subgroups had distinct features and potential therapeutic targets and were validated in external data sets. Interestingly, the TKR subgroup (which exists in both HR+ and HR- breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.

[Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics].

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics / 中国中药杂志

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

A Phytomolecule Icariin Protects from Sarcopenia Partially by Suppressing Myosin Heavy Chain Degradation in Orchiectomized Rats.

Treatments are lacking for sarcopenia, which is an age-related disease characterized by loss of skeletal muscle mass, strength, and/or physical performance. Icariin is a phytomolecule from herbal Epimedium, a traditional Chinese medicine widely used to treat musculoskeletal disorders for thousands of years. Here the effects of icariin against sarcopenia are investigated and the underlying mechanism is elucidated. A classic rat model of bilaterally orchiectomized (ORX) is used to induce sarcopenia. After administration for 8 weeks, compared to the control group, the forelimb grip strength, the specific tetanic forces of the soleus (SOL) and extensor digitorum longus muscle (EDL) are higher, and the fiber cross-sectional areas (CSAs) of the gastrocnemius and tibialis anterior muscle are larger in the icariin group. In addition, icariin promotes mRNA and protein expressions of myosin heavy chain (MyHC) both in SOL and EDL. Mechanistically, icariin significantly suppresses the mRNA and protein expressions of FOXO3a, atrogin-1, and MuRF-1, which are related to the degradation of myosin heavy chain. Collectively, icariin protects from sarcopenia in ORX rats characterized by enhancing grip strength and skeletal muscle contraction, as well as increasing skeletal muscle CSA by inhibiting the ubiquitination degradation of the MyHC in skeletal muscle fibers.

Alloimperatorin activates apoptosis, ferroptosis, and oxeiptosis to inhibit the growth and invasion of breast cancer cells in vitro.

Breast cancer is the most common malignant tumour in women. Our research on alloimperatorin from Angelica dahurica showed that alloimperatorin inhibited breast cancer cell viability in a concentration- and time-dependent manner; it also showed that apoptosis and ferroptosis inhibitors significantly weakened the antisurvival effect of alloimperatorin. Alloimperatorin clearly induced breast cancer cell apoptosis and increased the activities of caspase-3, caspase-8, caspase-9, and poly (ADP-ribose) polymerase; it also caused significant mitochondrial shrinkage, promoted the accumulation of Fe2+, reactive oxygen species, and malondialdehyde, and significantly reduced mRNA and protein expression levels of SLC7A11 and GPX4, indicating that alloimperatorin induces ferroptosis. In addition, alloimperatorin significantly promoted Kelch-like ECH-associated protein 1 (Keap1) expression; although it did not affect the expression of PGAM5 (mitochondrial serine/threonine protein phosphatase) and apoptosis-inducing factor mitochondria associated 1 (AIFM1), it significantly reduced the phosphorylation level of AIFM1. After downregulating the expression of Keap1, PGAM5, or AIFM1, the inhibitory effect of alloimperatorin on cell viability was significantly weakened, indicating that alloimperatorin regulates the Keap1/PGAM5/AIFM1 pathway to promote oxeiptosis. Alloimperatorin significantly inhibited the invasion of breast cancer cells, while Keap1 siRNA or GPX4 overexpression vectors significantly enhanced cell invasion and effectively reversed the anti-invasive effect of alloimperatorin. Therefore, alloimperatorin induces breast cancer cell apoptosis, ferroptosis, and oxeiptosis, thereby inhibiting cell growth and invasion.

Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice.

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 µmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.

Prognostic value of a positive-to-negative change in hormone receptor status after neoadjuvant chemotherapy in patients with hormone receptor-positive breast cancer.

BACKGROUND: To investigate the prognostic value of positive-to-negative changes in hormone receptor (HR) status after neoadjuvant chemotherapy (NCT) in patients with HR-positive breast cancer. METHODS: Data from 224 stage II-III breast cancer patients with positive HR status before NCT who had residual disease in the breast after NCT were collected. HR status of the residual tumors was retested after NCT. A survival analysis was performed in 214 patients with adjuvant endocrine therapy regardless of post-NCT HR status. The survival analysis also examined other clinical and pathologic variables. RESULTS: In total, 15.2 % of patients had a positive-to-negative change in HR status after NCT, and this change was observed more frequently in HER-2-positive tumors than HER-2-negative tumors (P = 0.001). In 214 patients who had been treated with adjuvant endocrine therapy regardless of post-NCT HR status, the alteration in HR status was an independent factor for the prediction of a poorer disease-free survival (P = 0.026) and overall survival (P < 0.001) in the adjuvant endocrine therapy patients. The 5-year disease-free survival and overall survival rates were 43.5 % and 59.8 %, respectively, in patients with HR status conversion and 67.8 % and 82.5 %, respectively, in patients whose HR status remained positive (log rank test P = 0.003 and P = 0.001). CONCLUSIONS: The switch of HR status after NCT is remarkable for HR-positive tumors. An HR-negative switch may identify patients who would benefit from alternative systemic therapies.

Adjuvant therapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and 5-fluorouracil.

We performed a retrospective study of 856 breast cancer patients in our hospital, to compare the therapeutic effect of pirarubicin with cyclophosphamide and 5-fluorouracil (CPF) with the standard epirubicin-based regimen (CEF) in adjuvant treatment of breast cancer. Patients were given cyclophosphamide and 5-fluorouracil 500 mg/m(2) each, and either pirarubicin 40 mg/m(2) or epirubicin 75-100 mg/m(2) , every 3 weeks, six cycles. A total of 233 patients used CPF and 623 patients used CEF regimen. The clinical and pathologic characteristics were well balanced between the two groups. The median follow-up time was 41 months, relapse-free survival (RFS) and overall survival (OS) were similar in both groups, p = 0.561 and p = 0.783, respectively. No treatment-related congestive heart failure or death was observed in either group. Regardless of chemotherapy regimens, only tumor size, lymph node status, and ER status were predictive factors in multivariate survival analysis. In stratified analysis, the total hazard ratio estimate for RFS was 0.876 (95% CI 0.561-1.369; p = 0.562), not in favor of either regimen, and no significant difference was observed in any subgroups between the two treatment arms. Our study verified that 3 weekly CPF gives the same efficacy and safety as the standard CEF; both CPF and CEF are the effective regimens that can be used in adjuvant chemotherapy of breast cancer.

Effect of pre-electroacupuncture on p38 and c-Fos expression in the spinal dorsal horn of rats suffering from visceral pain.

BACKGROUND: Acupuncture is an effective way to relieve pain, but the mechanism by which electroacupuncture (EA) decreases the visceral pain state still remains unclear. This study aimed to evaluate the effects of pre-electroacupuncture on pain behaviors, p38 phosphorylation, and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn of rats suffering from visceral pain. This study also investigated the probable signaling regulatory mechanism of the analgesic effect induced by electroacupuncture. METHODS: All rats were randomized into the control (Con) group, the Con + EA group, the visceral pain (VP) group, and VP + EA group (n = 8 for all groups). The visceral pain model was established using 40 microl of 5% formalin solution injected into the colon of rats. EA was applied to the bilateral Jiaji acupoints for 20 minutes before application of visceral pain. Parameters for EA were set at a continuous wave (20 Hz) and intensity where the rats shook their whiskers but did not scrabble (< or = 1 mA). The visceral pain score was recorded and the expressions of p38 and c-Fos protein were detected using Western blotting. Real-time quantitative PCR was also used to determine the expression of c-Fos mRNA. RESULTS: Rats in the VP group immediately presented with obvious visceral pain behaviors after being injected with formalin. p38 activity and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn were higher in the VP group than in the Con group (P < 0.05). By contrast, visceral pain behaviors were delayed in rats from the VP + EA group. p38 activity and c-Fos protein and mRNA expression were lower in the VP + EA group than that in the VP group (P < 0.01). CONCLUSIONS: Pre-electroacupuncture of the Jiaji acupoint has prophylactic analgesic effects on rats suffering from visceral pain. The p38 signal transduction pathway may be partly involved in the regulatory mechanism of this analgesic effect.

Effect of pre-electroacupuncture on p38 and c-Fos expression in the spinal dorsal horn of rats suffering from visceral pain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acupuncture is an effective way to relieve pain, but the mechanism by which electroacupuncture (EA) decreases the visceral pain state still remains unclear. This study aimed to evaluate the effects of pre-electroacupuncture on pain behaviors, p38 phosphorylation, and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn of rats suffering from visceral pain. This study also investigated the probable signaling regulatory mechanism of the analgesic effect induced by electroacupuncture.</p><p><b>METHODS</b>All rats were randomized into the control (Con) group, the Con + EA group, the visceral pain (VP) group, and VP + EA group (n = 8 for all groups). The visceral pain model was established using 40 microl of 5% formalin solution injected into the colon of rats. EA was applied to the bilateral Jiaji acupoints for 20 minutes before application of visceral pain. Parameters for EA were set at a continuous wave (20 Hz) and intensity where the rats shook their whiskers but did not scrabble (< or = 1 mA). The visceral pain score was recorded and the expressions of p38 and c-Fos protein were detected using Western blotting. Real-time quantitative PCR was also used to determine the expression of c-Fos mRNA.</p><p><b>RESULTS</b>Rats in the VP group immediately presented with obvious visceral pain behaviors after being injected with formalin. p38 activity and c-Fos protein and mRNA expression in both the colonic wall and spinal dorsal horn were higher in the VP group than in the Con group (P < 0.05). By contrast, visceral pain behaviors were delayed in rats from the VP + EA group. p38 activity and c-Fos protein and mRNA expression were lower in the VP + EA group than that in the VP group (P < 0.01).</p><p><b>CONCLUSIONS</b>Pre-electroacupuncture of the Jiaji acupoint has prophylactic analgesic effects on rats suffering from visceral pain. The p38 signal transduction pathway may be partly involved in the regulatory mechanism of this analgesic effect.</p>

Effect of detoxification, removing stasis and nourishing yin method on corticosteroid-induced hyperlipidemia in patients with systemic lupus erythematosus.

OBJECTIVE: To observe the effect of TCM therapy for detoxification, removing stasis, and nourishing yin on corticosteroid-induced hyperlipemia in patients with systemic lupus erythematosus (SLE), and to investigate its mechanism. METHODS: One hundred and seventy patients with SLE were randomly assigned to the integrative medicine group (IM group) and the Western medicine group (WM group), 85 in each group. Also, 30 healthy subjects selected from blood donors were enrolled in the normal control (NC) group. All patients were treated mainly with prednisone, while those in the IM group were given TCM therapy additionally, and the therapeutic course for both groups was 6 successive months. The changes of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and apolipoprotein A (ApoA) were determined and observed. A 2-year follow-up study was carried out in 16 patients of the WM group and 25 of the IM group. RESULTS: Before treatment, no significant difference had been found among the three groups in the serum levels of lipids and lipoproteins. After the 6-month treatment, as compared with the WM group, the IM group showed lower levels of TC, TG, LDL-C, and VLDL-C (P<0.05 or P<0.01) and higher levels of HDL-C and ApoA (P<0.05). A similar effect was also shown by the follow-up study in the IM group (P<0.05 or P<0.01). CONCLUSION: TCM therapy for detoxification, removing stasis, and nourishing yin can effectively regulate the levels of serum lipids and lipoproteins in preventing and treating SLE patients with corticosteroid-induced hyperlipemia.

Effect of emodin on pancreatic fibrosis in rats.

AIM: To establish the rats model of chronic fibrosing pancreatitis and to prove the anti-fibrotic effect of emodin in chronic pancreatitis with fibrosis. METHODS: Fifty rats were randomly divided into five groups, 10 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was infused into the pancreatic duct to induce chronic pancreatitis in rats (except for normal group). Emodin-treated rats were fed with different doses of emodin (20, 40 and 80 mg/kg body weight) for 28 d, while normal group and control group received 0.9% sodium chloride solution. Serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. Histopathological alterations were studied by optical microscopy. Expression of collagen was also examined while transforming growth factor-beta-1 (TGF-beta(1)) was localized by immunochemistry. RESULTS: In emodin-treated rats, the serum levels of HA and LN were decreased significantly (HA, 62.2 +/- 19.3 microg/L vs 112.7 +/- 26.5 microg/L, P < 0.05; LN 44.3 +/- 10.4 microg/L vs 86.2 +/- 16.5 microg/L, P < 0.05); the degree of fibrosis was ameliorated observably; the expression of collagen in pancreatic tissue was reduced especially in high-dose emodin-treated group (36% +/- 5% vs 42% +/- 6%, P < 0.05); with the increased doses of emodin, the expression of TGF-beta(1) was declined, compared with those in control group. CONCLUSION: Emodin has an anti-fibrotic effect on pancreatic fibrosis in rats. Because of its anti-fibrotic effect, it could be a potential herb for the treatment of chronic pancreatitis.

[Cytokines mechanism of shenfu injection in treatment of cardiogenic shock in canine].

OBJECTIVE: To investigate the effect of shenfu injection on canine with cardiogenic shock and the possible mechanism. METHOD: Cardiogenic shock model of canine was established by ligating left anterior descending (LAD) of coronary artery. The 15 canines with cardiogenic shock were randomly divided in to glucose injection group, shenfu injection group and sham-operated group. The hemodynamics parameters were monitored. Plasma TNF-alpha and IL-1beta levels were measured by radioimmunoassay. Expression of TNF-alpha mRNA and IL-1beta mRNA in myocardium were detected by RT-PCR. RESULT: Following cardiogenic shock, the mean artery pressure (MAP), left ventricular systolic pressure (LVSP), ventricular pressure rise ratio during systolic period (+ dp/dt(max)), and ventricular pressure decay ratio during diastolic period (- dp/dt(max)) decreased significantly; the plasma TNF-alpha and IL-1beta levels and the expression of TNF-a mRNA and IL-1beta mRNA in myocardium increased significantly. In shenfu injection group, MAP, LVSP and +/- dp/dt(max) increased significantly and plasma TNF-alpha and IL-1beta levels decreased significantly. In glucose injection group, MAP, LVSP, +/- dp/dt(max) and plasma TNF-alpha and IL-1beta levels had not changed significantly. The expression of TNF-alpha mRNA and IL-1beta mRNA in myocardium were significantly lower in shenfu injection group than those in glucose injection group. CONCLUSION: Shenfu injection probably can decrease over-exprssion of TNF-alpha mRNA and IL-1beta mRNA on transcription platform. Shenfu injection counteract cardiogenic shock, relieve myocardium damage and improve hemodynamics through inhibiting overproduction of TNF-alpha and IL-1beta.

Effect of detoxification, removing stasis and nourishing yin method on corticosteroid-induced hyperlipidemia in patients with systemic lupus erythematosus / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of TCM therapy for detoxification, removing stasis, and nourishing yin on corticosteroid-induced hyperlipemia in patients with systemic lupus erythematosus (SLE), and to investigate its mechanism.</p><p><b>METHODS</b>One hundred and seventy patients with SLE were randomly assigned to the integrative medicine group (IM group) and the Western medicine group (WM group), 85 in each group. Also, 30 healthy subjects selected from blood donors were enrolled in the normal control (NC) group. All patients were treated mainly with prednisone, while those in the IM group were given TCM therapy additionally, and the therapeutic course for both groups was 6 successive months. The changes of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and apolipoprotein A (ApoA) were determined and observed. A 2-year follow-up study was carried out in 16 patients of the WM group and 25 of the IM group.</p><p><b>RESULTS</b>Before treatment, no significant difference had been found among the three groups in the serum levels of lipids and lipoproteins. After the 6-month treatment, as compared with the WM group, the IM group showed lower levels of TC, TG, LDL-C, and VLDL-C (P<0.05 or P<0.01) and higher levels of HDL-C and ApoA (P<0.05). A similar effect was also shown by the follow-up study in the IM group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>TCM therapy for detoxification, removing stasis, and nourishing yin can effectively regulate the levels of serum lipids and lipoproteins in preventing and treating SLE patients with corticosteroid-induced hyperlipemia.</p>

[Effect of emodin on pancreatic fibrosis: experiment with rats].

OBJECTIVE: To study the effect of emodin on pancreatic fibrosis and potential mechanism thereof. METHODS: Fifty SD rats were randomly divided into 5 equal groups: normal control group, model control group, low-dose emodin-treated group, mediate-dose emodin-treated group, and high-dose emodin-treated group. The rats of the latter 4 groups underwent infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct so as to establish models of pancreatic fibrosis. The emodin-treated rats were fed with different doses of emodin (20, 40, and 80 mg/kg body weight), while the normal and model control groups received 0.9% sodium chloride solution instead. Twenty-eight days later the rats were killed, blood samples were collected, and their pancreases were taken out. The serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. The histopathological alterations were studied by optical microscopy. The expression of collagen was examined by Van Gieson staining. Western blotting was used to detect the protein expression of transforming growth factor-beta(1) (TGF-beta(1)). RESULTS: (1) The serum level of HA of the low-dose, mediate-dose, and high-dose emodin-treated groups were 87 microg/L +/- 22 microg/L, 78 microg/L +/- 25 microg/L, and 62 microg/L +/- 19 microg/L respectively, all significantly lower than that of the model control group (113 microg/L +/- 27 microg/L, P < 0.05 or < 0.01). The serum levels of laminin in the low-dose, mediate-dose, and high-dose emodin-treated groups were 67 microg/L +/- 14 microg/L, 57 microg/L +/- 12 microg/L, and 44 microg/L +/- 10 microg/L respectively, all significantly lower than that of the model control group (86 microg/L +/- 17 microg/L, P < 0.05 or P < 0.01); (2) The degrees of fibrosis of the emodin-treated groups were obviously ameliorated in comparison with the model control group, the higher the dose of emodin the more improved the pathological changes, especially in the high-dose emodin-treated group (P < 0.05). (3) The percentages of collagen positive cells of the low-dose, mediate-dose, and high-dose emodin-treated groups were 39% +/- 7%, 38% +/- 4%, and 36% +/- 5% respectively, all lower than that of the model control group (42% +/- 6%), with a significant difference between the high-dose emodin-treated group and the model control group (P < 0.05). (4) The protein content of TGF-beta(1) of the low-dose, mediate-dose, and high-dose emodin-treated groups were 44.3% +/- 2.1%, 39.2% +/- 1.8%, and 28.8% +/- 1.6% respectively, all significantly lower than that of the model control group (60.7% +/- 1.7%, all P < 0.05), and the protein content of TGF-beta(1) of the high-dose emodin-treated group was significantly lower than those of the other 2 emodin-treated groups (both P < 0.05). CONCLUSION: Emoidn has an anti-fibrosis effect on pancreatic fibrosis, which maybe related to the content of TGF-beta(1) protein.