PMID: 

Biochem Pharmacol. 2020 Jan 24:113824. Epub 2020 Jan 24. PMID: 31987852

Abstract Title: 

Using curcumin to turn the innate immune system against cancer.

Abstract: 

Curcumin has been at the center of vigorous research and major debate during the past decade. Inspired by its anti-inflammatory properties, many curcumin-based products are being sold now to manage various forms of arthritis. Parallel preclinical studies have established its role in dissolving beta-amyloid plaques, tau-based neurofibrillary tangles, and also alpha-synuclein-linked protein aggregates typically observed in Parkinson's disease. In cancer research, most cancer cells in culture are eliminated by curcumin at an IC50 of 15-30 µM, whereas the maximum in vivo curcumin concentration achieved in humans is only about 6 µM. Additionally, a decade ago, no improvement over the placebo groups was observed in clinical studies using free curcumin as an anticancer agent. The lack of anticancer efficacy was attributed to its lowbioavailability, which results from the low water-solubility and high metabolic rate in vivo. Newer lipid-complexed or antibody-targeted forms have been used and these studies have revealed an exciting property of curcumin, which involves repolarization of the tumor-promoting, tumor-associated microglia/macrophages (TAMs) into a tumoricidal form and recruitment of natural killer cells from the periphery. This review will cover some efforts to explore the effect of appropriately-delivered curcumin to dramatically alter the tumor microenvironment, thereby launching an indirect attack on the tumor cells and the tumor stem cells. Reviewing some aspects of immunotherapy, this article will argue for the use of the innate immune cells in cancer therapy.

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PMID: 

Biomed Pharmacother. 2020 May ;125:109946. Epub 2020 Jan 28. PMID: 32004976

Abstract Title: 

Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice.

Abstract: 

OBJECTIVES: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.METHODS: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested.RESULTS: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.CONCLUSIONS: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

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PMID: 

S Afr Med J. 1980 Dec 13 ;58(24):974-7. PMID: 7444701

Abstract Title: 

The effect of ascorbate on cellular humoral immunity in asthmatic children.

Abstract: 

Ten White children with bronchial asthma and exercise-induced bronchoconstriction were assessed immunologically before and 1, 3 and 6 months after the commencement of standard therapy supplemented with ascorbate 1 g/d. The tests of cellular immune function were neutrophil chemotaxis, phagocytosis and resting and stimulated nitroblue tetrazolium reduction, and lymphocyte mitogen-induced transformation. Humoral functions measured were secretory IgA, serum immunoglobulins, alpha 1-antitrypsin, C3, C4 and total haemolytic complement, antistreptolysin O (ASO) and C-reactive protein. Radio-allergosorbent testing to the common allergens Cynodon dactylon (grass), Dermatophagoides pteronyssinus (mite), house dust and cat epithelium was performed on each child before and 3 and 6 months after treatment. Two children had depressed neutrophil motility, 4 had depressed lymphocyte transformation, and 7 had elevated levels of ASO. These functions normalized after 6 months of ascorbate-supplemented therapy. Serum total IgE levels but not specific IgE levels were likewise reduced after 6 months of therapy. Reduced levels of serum alpha 1-antitrypsin were observed in 2 children, and remained unchanged throughout the study.

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PMID: 

Complement Ther Med. 2018 Jun ;38:11-18. Epub 2018 Mar 26. PMID: 29857875

Abstract Title: 

Protective role of flavonoid baicalin from Scutellaria baicalensis in periodontal disease pathogenesis: A literature review.

Abstract: 

INTRODUCTION: Periodontal disease is characterized by a chronic infection, leading to the irreversible destruction of tissues supporting the teeth. Bacteria, pro-inflammatory mediators and host immune response play important role in the progress of periodontal disease. Baicalin is a bioactive flavone extracted from the dry raw root of Scutellaria baicalensis, with pharmaceutical actions of anti-inflammation, anti-oxidants, anti-tumor, antivirus, and so on. The present review summarizes the efficacy of baicalin in periodontal treatment.METHODS: A computer-based literature search was carried out using Pubmed, Scopus and Web of Science to identify papers published until 2017. Keywords used in the search were"baicalin"/"baicalein"and various words related to periodontal disease (periodontal, periodontitis, periodontal tissue, gingival, gingivitis, gingival tissue, periodontal disease, gingival disease, gingiva, periodontium).RESULTS: A total of 28 original studies were found, including 3 bacteriological studies, 7 zoological studies and 18 cytological studies. 15 of them were published in English and 13 of them were published in Chinese. Results from these 28 studies could not be pooled to conduct meta-analysis due to the heterogeneity. The pharmacological properties and mechanisms of baicalin for treating periodontal disease is mainly focused on five aspects: antibacterial effect on putative periodontopathic bacteria, protective effect on periodontal tissues, regulatory effect on pro-inflammatory mediators and matrix metalloproteinases, and regulatory effect on innate immune response.CONCLUSIONS: Baicalin have been shown to possess multiple pharmacological activities in periodontal tissues. However, the underlying mechanisms have not been fully defined. Further researches are needed to provide more scientific evidence for the clinical periodontal treatment.

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PMID: 

J Nat Med. 2018 Jun ;72(3):655-666. Epub 2018 Mar 14. PMID: 29542003

Abstract Title: 

Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway.

Abstract: 

Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Amice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-Amice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element bindingprotein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.

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PMID: 

Int Immunopharmacol. 2015 Dec ;29(2):269-277. Epub 2015 Nov 11. PMID: 26578286

Abstract Title: 

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach.

Abstract: 

Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2018 Mar ;43(6):1235-1240. PMID: 29676134

Abstract Title: 

[Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis].

Abstract: 

This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg⁻¹ BW, which was combined withtherectal administration with three doses of supercritical extracts (15, 30, 60 g·kg⁻¹ BW). PCNA, 8-oxoguaine, γ-H2AX, iNOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolicacids and supercritical extracts from A. sinensis suppressed the tumor growth and cell proliferation, and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.

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PMID: 

J Tradit Complement Med. 2012 Jul ;2(3):235-41. PMID: 24716138

Abstract Title: 

Anti-anxiety Activity of Methanolic Extracts of Different Parts of Angelica archangelica Linn.

Abstract: 

Angelica archangelica Linn.is a herb distributed in tropical and subtropical regions of the world. In Indian and Chinese system of medicine, it is used for nervous disorders and cerebral diseases. Previously the aqueous extract of the A. archangelica was evaluated for anxiolytic activity and was found to have significant potential for the same. The present study is aimed to evaluate the anxiolytic activity of methanol extract of root (MER), stem (MES), leaf (MEL), fruit (MEF) and whole plant (MEW) of Angelica archangelica Linn. All the extracts (MER, MES, MEL, MEF and MEW) were evaluated for anxiolytic effects using elevated plus maze test (EPM) model in rats. Methanol extracts of different parts of A.archangelica had increased number of entries and time spent in open arms while they decreased the number of entries and duration of time spent in closed arm of the EPM. In a similar fashion, the diazepam increased the percentage of time spent and percentage of arm entries in the open arms (*P

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PMID: 

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10 ;40:180-6. Epub 2012 Aug 29. PMID: 22960104

Abstract Title: 

Coumarins from Angelica archangelica Linn. and their effects on anxiety-like behavior.

Abstract: 

UNLABELLED: TRADITIONAL RELEVANCE: Angelica archangelica Linn. (Apiaceae) is an herb distributed in tropical and subtropical regions of the world. Both in Chinese and Indian system of medicine, it is used for nervous disorders including anxiety, anorexia, migraine and other cerebral diseases.AIM OF STUDY: To evaluate the anxiolytic potential of non polar coumarins isolated from A. archangelica Linn.METHODS AND RESULTS: A. archangelica Linn. (1 kg) was subjected to extraction in a soxhlet apparatus with petroleum ether (40-60°C), yield 6.9% w/w. The extract of petroleum ether produced a yellow colored precipitate (YP) which was evaluated for anxiolytic like effect using EPM test and was found significant (**P

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PMID: 

Food Chem Toxicol. 2017 Nov ;109(Pt 2):1026-1031. Epub 2017 May 6. PMID: 28487231

Abstract Title: 

Antiviral effect of compounds derived from Angelica archangelica L. on Herpes simplex virus-1 and Coxsackievirus B3 infections.

Abstract: 

The dichloromethane extract from fruits of Angelica archangelica L. was separated by the modern high-performance countercurrent chromatography (HPCCC). The extract and five pure compounds: xanthotoxin, bergapten, imperatorin, phellopterin and isoimperatorin, and the mixture of imperatorin and phellopterin, have been studied as the potential antiviral agents against Herpes simplex virus type l and Coxsackievirus B3. The cytotoxicity was measured using the MTT method. Compounds were tested for the in vitro antiviral activity using the cytopathic effect (CPE) inhibitory assay and by the virus titre reduction assay. Real-time PCR was used to quantify the relative inhibition of the HSV-1 replication. The results indicate that the highest activity was demonstrated by the extract, imperatorin, phellopterin and the mixture of imperatorin and phellopterin, reducing the HSV-1 replication by 5.61 log, 4.7 log, 3.01 log and 3.73 log, respectively. The influence of isolated compounds on the CVB3 replication was not significant. Only the extract caused the decrease in the titre of virus in relationto the virus control. Our results show that coumarins of A. archangelica L. might be a potential candidate for the development of the alternative natural anti- HSV-1 compound. Moreover, the presence of isopentenyloxy moiety at C-8 position significantly improves their activity.

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