Gut microbiota as a target for traditional Chinese medicine in the treatment of cardiovascular disease: potential mechanisms and therapy strategies / 药学学报

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

Strategy and challenge of innovative drug research and development from clinically effective ingredients of traditional Chinese medicine / 中国中药杂志

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS / 中国天然药物

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats / 中国中药杂志

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Metabolomics and its application in the treatment of coronary heart disease with traditional Chinese medicine / 中国天然药物

Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.

Establishment of a quantitative real-time PCR for rapid detection of Panax quinquefolius / 中国中药杂志

In this study, the specific primers and probes of Panax quinquefolius were designed for a quantitative real-time PCR, and the rapid identification method of P. quinquefolius was established by optimizing conditions. The method was used to validate 43 samples of the traditional Chinese medicine,and the results showed that 22 samples of P. quinquefolius were identified accurately. The limit of detection of the method can be reach to 1×10⁻⁴ ng. The method is accurate, fast, sensitive and specifically.

Application of network biology on study of traditional Chinese medicine / 中国中药杂志

With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine.

Chemical constituents from ethyl acetate-soluble extraction of Valeriana jatamansi / 中国中药杂志

Application of a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, led to the isolation of 173 compounds including irdidoids, monoterpenes, sesquiterpenes, triterpenes, lignans, flavonoids, and simple aromatic derivatives from the ethyl acetate-soluble fraction of the whole plants of Valeriana jatamansi(Valerianaceae), and their structures were elucidated by spectroscopic methods including 1D, 2D NMR UV, IR, and MS techniques. Among them, 77 compounds were new. In previous reports, we have described the isolation, structure elucidation, and bioactivities of 68 new and 25 known compounds. As a consequence, we herein reported the isolation and structure elucidation of the remaining 9 new and 71 known compounds, the structure revision of valeriotriate A(8a), as well as cytotoxicity of some compounds.

An updated role of astragalosideⅣin heart failure / 中国药理学与毒理学杂志

Heart failure has become a global public health problem that seriously threatens human health. Due to "multi-target" effect, traditional Chinese medicine has unique advantages in the treat-ment of heart failure. Astragaloside Ⅳ is one of the main active ingredients of astragalus membrana-ceus.It has the functions of protecting the heart and neovascularization,anti-inflammation,anti-oxida-tion, regulating energy metabolism, neuroprotection and anti-cancer effects. This article reviews the recent progresses of astragaloside Ⅳ in the treatment of heart failure.Data show that astragaloside Ⅳcan inhibit heart fibrosis,attenuate excessively activation of renin-angiotensin system,increase energy metabolism, promote positive inotropic action, inhibit myocardial cell apoptosis, etc, which are all involved in the protective role of astragaloside Ⅳ in rodents or cellular models of heart failure.Astragalo-side Ⅳ may be a potential active ingredient in traditional Chinese medicine for the treatment of heart failure.

Pharmacokinetics of five ginsenosides of Shexiang Baoxin pill in plasma of myocardial infarction rats / 中国中药杂志

Shexiang Baoxin pill(SBP) is widely used for treating coronary heart disease in clinic, with ginsenosides as its main effective component. This study was designed to investigate and compare the pharmacokinetic characteristics of five ginsenosides of five compounds after multiple oral administrations, ginseng extract(GE) and SBP in myocardial infarction rats. After intragastric administration to myocardial infarction rats, the plasma samples were analyzed by liquid chromatography tandem triple-quad mass spectrometry. The results showed that Cmax of five compounds in all groups were less than 200 μg•L⁻¹. Tmax of corresponding analytes between groups revealed that ginsenosides in both SBP and GE were absorbed faster than each of the five compounds, indicating that GE and compounds contain components promoting absorption of ginsenosides. The oral administration doses of ginsenosides in SBP were the least in all groups, but with the greatest AUC0-tand AUCINF, which indicated that ginsenosides in SBP had the best absorption in all groups after oral administration to myocardial infarction rats. This study also demonstrated that compound is the best form of traditional Chinese medicine.

Interaction of effective ingredients from traditional Chinese medicines with intestinal microbiota / 中国中药杂志

A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques.

"Omics" in pharmaceutical research: overview, applications, challenges, and future perspectives / 中国天然药物

In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.

Isochamaejasmin induces apoptosis in leukemia cells through inhibiting Bcl-2 family proteins / 中国天然药物

The biflavonoid isochamaejasmin is mainly distributed in the root of Stellera chamaejasme L. (Thymelaeaceae) that is used in traditional Chinese medicine (TCM) to treat tumors, tuberculosis, and psoriasis. Herein, isochamaejasmin was found to show similar bioactivity against Bcl-2 family proteins to the reference Bcl-2 ligand (-)-gossypol through 3D similarity search. It selectively bound to Bcl-xl and Mcl-1 with Ki values being 1.93 ± 0.13 μmol·L(-1) and 9.98 ± 0.21 μmol·L(-1), respectively. In addition, isochamaejasmin showed slight growth inhibitory activity against HL-60 with IC50 value being 50.40 ± 1.21 μmol·L(-1) and moderate growth inhibitory activity against K562 cells with IC50 value being 24.51 ± 1.62 μmol·L(-1). Furthermore, isochamaejasmin induced apoptosis of K562 cells by increasing the intracellular expression levels of proteins of the cleavage of caspase-9, caspase-3, and PARP which involved in the Bcl-2-induced apoptosis pathway. These results indicated that isochamaejasmin induces apoptosis in leukemia cells by inhibiting the activity of Bcl-2 family proteins, providing evidence for further studying the underlying anti-cancer mechanism of S. chamaejasme L.

Study on the mechanism of polypeptide extract from scorpion venom on inhibition of angiogenesis of H 22 hepatoma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of polypeptide extract from scorpion venom (PESV) on inhibiting angiogenesis.</p><p><b>METHODS</b>The H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor-bearing mice were randomly divided into 4 groups, i.e., the control group, the high dose PESV group, the low dose PESV group, and the 5-fluorouracil (5-Fu) group, 10 mice in each group. The intervention was lasted for 14 days. The growth curve of the tumor volume was drawn and the inhibition rate calculated. Pathological changes of the tumors were observed by HE staining. The microvessel density (MVD) was detected using SP method. The protein expression levels of phosphatidylinositol 3-kinase (P13K), phosphoprotein kinase B (P-Akt), hypoxia-inducible factor-1 alpha (HIF-1 )alpha, and vascular endothelial growth factor-A (VEGF-A) were detected by immunohistochemical assay and Western blot.</p><p><b>RESULTS</b>The tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high dose PESV group, and the low dose PESV group. Compared with the control group, the protein expression of PI3K, P-Akt, HIF-1alpha, and VEGF-A were obviously inhibited by PESV and 5-Fu (P <0. 05,P <0. 01). The MVD also decreased in the high and low dose PESV groups (P < 0.05).</p><p><b>CONCLUSIONS</b>PESV could inhibit the angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing the expression of PI3K, P-Akt, HIF-1 alpha, and VEGF-A.</p>

Efficacy and safety evaluation of fire needling for rats with rheumatoid arthritis / 中国针灸

<p><b>OBJECTIVE</b>To explore the therapeutic effect and safety of fire needling on rat with rheumatoid arthritis.</p><p><b>METHODS</b>Forty female Wistar rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group and a fire needling group, 10 rats in each group. The 0.1 mL of normal saline was subcutaneously injected in rat's right back paw in the normal group, while the other groups received subcutaneous injection of 0.1 mL of complete Freund's adjuvant to establish the model. The pricking method was applied in the fire needling group at "Jiaji" (EX-B 2), "Zusanli" (ST 36) and Ashi points with a depth of 5 mm, once every three days, and totally eight times were required. In the MTX group, with intragastric administration of 2.0 mg/kg per rat, the treatment was given once every seven days, and totally four times were required. The weight, swelling rate of foot, joint pain score and polyarthritis index of rats in each group as well as the pathological change of liver tissue under light microscope were observed.</p><p><b>RESULTS</b>The weight, swelling rate of foot, joint pain score and polyarthritis index in the model group were significantly higher than those in the normal group (P < 0.05, P < 0.01), after the treatment, the above-mentioned indexes in the two treatment groups were obviouly dereased as componed with those in the model group (all P < 0.01), and there were statistical differences between the fire needling group and MTX group (P < 0.05, P < 0.01). Compared with the normal group, inflammatory cells were appeared with a cluster distribution in the liver cells of rats in the model group. The inflammatory cells were reduced in the MTX group and fire needling group, and liver cells had degenerative edema and cell nucleus were largen and deformed in the MTX group.</p><p><b>CONCLUSION</b>The fire needling has significant efficacy for rats with adjuvant arthritis (AA) without any damage to the liver, which coud have a better control of disease progression of rheumatoid arthritis .</p>

Effect of acupuncture on serum MIP-2 and MIP-2 mRNA expressions in isolated Fei and Dachang of severe acute pancreatitis induced acute lung injury rats in the acute phase / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe effect of acupuncture on serum macrophage inflammatory protein-2 (MIP-2) and MIP-2 mRNA expressions in isolated Fei and Dachang of severe acute pancreatitis (SAP) induced acute lung injury (ALI) rats in the acute phase.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into four groups, i.e., the sham-operation group, the SAP group, the acupuncture treatment group, and the acupuncture control group, 10 in each group. The SAP model was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatobiliary duct. Under the guidance of "Fei and Dachang exterior-inferiorly related", points were acupunctured along Fei, Dachang, and Pi channels, as well as those points on the back of rats in the acupuncture treatment group 0.5 h after modeling. Besides, points were acupunctured along Fei and Pi channels, as well as those points on the back of rats in the acupuncture control group 0.5 h after modeling. Serum levels of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO), and MIP-2 expressions were examined 6 h after modeling. Expressions of MIP-2 mRNA in isolated lung and large intestine tissues were detected by reverse transcription PCR.</p><p><b>RESULTS</b>Compared with the sham-operation group, serum levels of TNF-alpha and NO, and expressions of MIP-2 and MIP-2 mRNA in isolated lung and large intestine tissues were significantly higher in the SAP group (P < 0.05). Each index was lower in the acupuncture treatment group than in the SAP group and the acupuncture control group (P < 0.05). Besides, the serum level of MIP-2 and the MIP-2 mRNA expression in isolated lung and large intestine tissues were positively correlated in all groups except the sham-operation group (P < 0.05).</p><p><b>CONCLUSIONS</b>Under the guidance of "Fei and Dachang exterior-inferiorly related", acupuncture could remarkably reduce the severity of SAP induced ALI rats in the acute phase. Its mechanism might be related to suppressing over-expressions of MIP-2 mRNA in isolated lung and large intestine tissues, and lowering the serum MIP-2 expression level.</p>

Application of small molecule compounds inducing differentiation of stem cells / 药学学报

With the development of stem cells and regenerative medicine (treatment of various diseases using stem cells) research, the induction of differentiation of human stem cell technology has also made significant progress. The development of chemical biology offers a variety of small biological molecules for stem cell biology. This review focuses on how small molecule compounds (natural and synthetic) induce differentiation of stem cells.

Treatment of facial pigmentation after burns with traditional Chinese medicine mask and skin care / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the effects of traditional Chinese medicine mask combined with skin care in the treatment of facial pigmentation after burns.</p><p><b>METHODS</b>Forty-one patients with facial pigmentation after burns hospitalized from January 2009 to June 2010 were enrolled and divided into treatment group (n = 26, odd number) and control group (n = 15, even number) according to the visiting order. After cleaning, massaging, and steam spraying to faces, patients in treatment and control groups were respectively treated with traditional Chinese medicine mask developed by physicians in our hospital and common commercial beauty mask. Masks were removed when they became completely dry. The treatment was repeated every other day. Ten times made up a course of treatment. Three consecutive courses were carried out on each patient. Before treatment and at the end of each course, the skin color differences were measured with Vancouver Pigmented Scar Scale; image gray scale value of pigmented skin was measured with image analysis technique. Satisfaction degree acknowledged by both patients and physicians were recorded at the end of each course; adverse effects were recorded; and the overall efficacy between two groups was compared. Data were processed with chi-square test or t test.</p><p><b>RESULTS</b>Skin color differences, image gray scale value of patients in treatment group were close to those in control group before treatment (with t value respectively 0.800 and 0.694, P values all above 0.05). Skin color differences, image gray scale value, and satisfaction degree acknowledged by both patients and physicians in treatment group were better than those in control group at the end of each course. At the end of the third course of treatment, the skin color differences in treatment and control groups scored 0.5 ± 0.4 and 1.1 ± 0.6, respectively, with image gray scale value of 55 ± 5 and 66 ± 6, respectively, which were statistically different from each other (with t value respectively 3.389 and 5.102, P values all below 0.01). The overall efficacy of the treatment group was 92.3%, which was much better than that of the control group (53.3%, χ(2) = 6.31, P < 0.05). No allergy caused by the traditional Chinese medicine mask was observed during the treatment.</p><p><b>CONCLUSIONS</b>The traditional Chinese medicine mask combined with skin care is effective for the treatment of facial pigmentation after burns.</p>

Treatment of chronic allograft nephropathy with combination of enalapril and bailing capsule / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of combined use of enalapril (an angiotensin converting enzyme inhibitor, ACEI) and Bailing Capsule (a Chinese herbal preparation made by fermented cordyceps sinensis, BLC) on renal function in patients with chronic allograft nephropathy (CAN) for seeking an effective therapy to control CAN progression.</p><p><b>METHODS</b>Eighty-four CAN patients were randomly assigned to four groups, the 22 patents in group A treated with combined treatment of enalapril (10 mg/d) and BLC (2.0 g, twice a day); 20 in group B with enalapril alone; 21 in group C with BLC alone; and 21 in group D with the previously used immunosuppressive agents for control. Levels of serum creatinine (SCr), blood urea nitrogen (BUN), clearance of creatinine (CCr), 24 h urinary protein (24 h Upro) and urinary transforming growth factor beta1 (TGF-beta1) in all patients were measured before treatment, and after 6-and 9-month treatment.</p><p><b>RESULTS</b>CCr was improved in patients of group A after 6-month treatment accompanied with decrease of SCr, 24 h Upro and urinary TGF-131 (P < 0.05), the latter 3 indexes were lower than in group D, and there was no difference among group A-C. These indexes in patients of group A, B, and C were further improved after treatment for 9 months (P < 0.01), whereas they worsened in patients of group B (P < 0.05). and the cases of patients with renal function improving or stable condition were more in group A than those in group B.</p><p><b>CONCLUSION</b>Combined treatment of enalapril and BLC has better efficacy than using enalapril or BLC alone in reducing excretion of urinary protein, improving or stabilizing the function of graft kidney, and retarding CAN progression.</p>

The anti-fibrotic effects of Qidan granule in experimental silicosis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the anti-fibrotic effects of Qidan granule in rats.</p><p><b>METHODS</b>The rats were randomly divided into six experimental groups: normal group, model group, Qidan group, Tetrandrine group. All rats except normal group were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. Qidan group and Tetrandrine group were treated with Qidan granule (3125 mg/kg) or treated with Tetrandrine (22 mg/kg) respectively. All the rats were sacrificed after 5 months. Calculate Lung/body coefficient by weighting the lung wet weight and the body weight of rats. Content of Hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 was examined by using enzyme-linked immunosorbent assay (ELISA). Paraffin embedded lung sections with HE staining, VG staining and Gomori staining were observed under light microscope.</p><p><b>RESULTS</b>In Qidan group and Tetrandrine group, Lung/body coefficient and content of Hydroxyproline and expression of transforming growth factor-beta1 were lower as compared with model group (P < 0.05). Model group mainly showed III approximately IV grade silicotic nodule, which contained thick collagen and sparse reticulum fibe; Qidan group and Tetrandrine group appeared with II grade silicotic nodule, which contained tiny collagen and intensive reticulum fibe. Tetrandrine group showed injury of kidney, and others were normal.</p><p><b>CONCLUSION</b>Qidan granule extract should prevent and from inhibit the remarkably silicotic fibrosis in rats.</p>