Anti-inflammatory Herbal Medicine Research Articles

Anti-Inflammatory Effect of Meriania hexamera Sprague by Targeting Syk Kinase in NF-κB Signaling.

Inflammation is a protective mechanism against harmful stimuli. There are two types of inflammation, acute and chronic, and severe diseases such as cardiovascular disease and cancer can be caused by chronic inflammation. Therefore, this research was conducted to discover new anti-inflammatory drugs. Meriania hexamera Sprague is a common herb in the Amazon region in South America. It is used as a traditional medical herb by natives, but no studies to date have investigated its anti-inflammatory activity. Using lipopolysaccharide (LPS), pam3CSK4 (Pam3), and poly(I:C), we studied the M. hexamera Sprague-Methanol Extract's (Mh-ME) in vitro anti-inflammatory functions. Using RAW264.7 cells, we detected the released nitric oxide (NO) and mRNA expression extent of inducible nitric oxide synthase (iNOS) with pro-inflammatory proteins like tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and iterleukin-1 beta (IL-1β). It was found that Mh-ME suppressed the inflammatory activities in a dose-dependent manner. In the luciferase assay, the nuclear factor kappa light chain enhancer of the activated B cells (NF-κB) pathway was inhibited by Mh-ME. Mh-ME especially acted as an inhibitor of Syk kinase according to the results from CETSA. We also confirmed that Mh-ME mitigates acute gastritis derived from HCl/EtOH in ICR mice, ameliorating the expression of IL-1β and tumor necrosis factor-alpha (TNF-α). In conclusion, Mh-ME is an herb with anti-inflammatory effects that targets Syk in the NF-κB pathway, suggesting that Mh-ME could be used as an anti-inflammatory herbal medicine.

Discovery, Validation, and Target Prediction of Antibacterial and Antidiabetic Components of Archidendron clypearia Based on a Combination of Multiple Analytical Methods.

Archidendron clypearia (A. clypearia), a Fabaceae family member, is widely used as an anti-inflammatory herbal medicine; however, its antibacterial and antidiabetic properties have not been extensively investigated. This study aimed to systematically analyze the antibacterial and antidiabetic components of A. clypearia by utilizing a combination of analytical methods. First, ten different polarity extracts were analyzed through ultra-performance liquid chromatography (UPLC), and their antibacterial and antidiabetic activities were evaluated. Then the spectrum-effect relationship between the biological activity and UPLC chromatograms was analyzed by partial least squares regression and gray relational analysis, followed by corresponding validation using isolated components. Finally, network pharmacology and molecular docking were implemented to predict the main antibacterial target components of A. clypearia and the enzyme inhibition active sites of α-amylase and α-glucosidase. P15, P16, and P20 were found to be the antibacterial and antidiabetic active components. The inhibitory effect of 7-O-galloyltricetiflavan (P15) on six bacterial species may be mediated through the lipid and atherosclerosis pathway, prostate cancer, adherens junctions, and targets such as SRC, MAPK1, and AKT1. The molecular docking results revealed that 7-O-galloyltricetiflavan and 7,4'-di-O-galloyltricetiflavan (P16/P20) can bind to α-amylase and α-glucosidase pockets with binding energies lower than -6 kcal/mol. Our study provides guidance for the development of antibacterial and antidiabetic products based on A. clypearia and can be used as a reference for the evaluation of bioactivity of other herbs.

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

Knee osteoarthritis (KOA) is an increasingly prevalent heterogeneous disease characterized by cartilage erosion and inflammation. As the main chemical constituent of Angelicae Pubescentis Radix (APR), an anti-inflammatory herbal medicine, the potential biological effects and underlying mechanism of osthole on chondrocytes and KOA progression remain elusive. In this study, the potential effect and mechanism of osthole on KOA were investigated in vitro and in vivo. We found that osthole inhibited IL-1β-induced apoptosis and cartilage matrix degeneration by activating autophagy in rat chondrocytes. In addition, osthole could activate autophagy through phosphorylation of AMPK/ULK1, and AMPK serves as a positive upstream regulator of ULK1. Furthermore, KOA rats treated with osthole showed phosphorylation of the AMPK/ULK1 pathway and autophagy activation, as well as cartilage protection. Collectively, the AMPK/ULK1 signaling pathway can be activated by osthole to enhance autophagy, thereby suppressing KOA development. Osthole may be a novel and effective therapeutic agent for the clinical treatment of KOA.

Proposed Marketing Strategy of New Product: Case of Anti-Inflammatory Herbal Medicine for Ganeshfit Company

Herbal medicines are growing in the global market as global health awareness is increasing. The global market potential of this herbal medicine also has an impact on the development of the product market in Indonesia. New herbal medicinal product innovations are emerging. Ganeshfit Company Research and Development Team develops anti-inflammatory herbal medicinal products that have a safer long-term effect. The development of new products requires the right marketing strategy to enter the market. To find out the right strategy, the company can conduct an internal analysis of the company itself and conduct an external analysis for the industry as a whole. Therefore, the purpose of this research is to find out business solutions for Ganeshfit Companies, especially in terms of marketing strategies. To formulate recommendations and conclusions, this research will use mixed methods to gain insight and achieve goals. The research will be conducted in three phases. The first phase of the analysis is an analysis of the literature on competitors, internal, and external to the company. The second phase is the collection of qualitative data (through interviews with 5 key users) to determine consumer considerations. The last is the collection of quantitative data (a questionnaire with 177 respondents) to verify the results of the data obtained from the collection of qualitative data. The framework used for external analysis is PESTEL analysis, Porter's Five Forces analysis and Porter's Generic Strategy. For internal analysis, the frameworks used are SWOT analysis and VRIO analysis. To formulate a potential marketing strategy, this study also uses a simple marketing model from Kotler which includes market segmentation, targeting, positioning, and marketing mix.

An Optimized Two-Herb Chinese Food as Medicine Formula Reduces Cisplatin-Induced Nephrotoxicity in the Treatment of Lung Cancer in Mice.

Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients’ confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.

Sinoacutine inhibits inflammatory responses to attenuates acute lung injury by regulating NF-\u03baB and JNK signaling pathways

BackgroundStephania yunnanensis H. S. Lo is widely used as an antipyretic, analgesic and anti-inflammatory herbal medicine in SouthWest China. In this study, we investigated the anti-inflammatory activity and mechanism of sinoacutine (sino), one of the primary components extracted from this plant.MethodsA RAW264.7 cell model was established using lipopolysaccharide (LPS) induced for estimation of cytokines in vitro, qPCR was used to estimate gene expression, western blot analysis was used to estimate protein level and investigate the regulation of NF- κB, JNK and MAPK signal pathway. In addition, an acute lung injury model was established to determine lung index and levels of influencing factors.ResultsUsing the RAW264.7 model, we found that sino reduced levels of nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and prostaglandin E2 (PGE2) but increased levels of IL-6. qPCR analysis revealed that sino (50, 25 μg/ml) inhibited gene expression of nitric oxide synthase (iNOS). western blot analysis showed that sino significantly inhibited protein levels of both iNOS and COX-2. Further signalling pathway analysis validated that sino also inhibited phosphorylation of p65 in the NF-κB and c-Jun NH2 terminal kinase (JNK) signalling pathways but promoted the phosphorylation of extracellular signal regulated kinase (ERK) and p38 in the MAPK signalling pathway. In addition, in a mouse model induced by LPS, we determined that sino reduced the lung index and the levels of myeloperoxidase (MPO), NO, IL-6 and TNF-α in lung tissues and bronchoalveolar lavage fluid (BALF) in acute lung injury (ALI).ConclusionTaken together, our results demonstrate that sino is a promising drug to alleviate LPS-induced inflammatory reactions.

The Potential of Vouacapanes from Pterodon emarginatus Vogel Against COVID-19 Cytokine Storm.

Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In this study, the mechanisms underlying the anti-inflammatory activity of P. emarginatus oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. Results: Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin 6 (IL-6) was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. Conclusion: The results support the ethnomedicinal use of P. emarginatus oleoresin as an anti-inflammatory herbal medicine, and also highlight P. emarginatus oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, cyclooxygenase-2 (COX-2), phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.

Effectivity of Anredera cordifolia Leaf Extract and Vitamin E as a Candidate of Antiinflammatory Herbal Medicine on Animals Model with Acute Postpartum Metritis Based on TNF-a Level and Histopathology of Inflammatory Cells in Endometrium

Effectivity of Anredera cordifolia Leaf Extract and Vitamin E as a Candidate of Antiinflammatory Herbal Medicine on Animals Model with Acute Postpartum Metritis Based on TNF-a Level and Histopathology of Inflammatory Cells in Endometrium

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Oroxylum indicum Kurz (L.) seed extract exerts antioxidant and anti-inflammatory effects on lipopolysaccharide-stimulated BV2 microglial cells

Background: Oroxylum indicum (L.) Kurz is a plant that has been extensively used as the traditional medicine in several Asian countries. However, the role of Oroxylum indicum seeds (OISs) in the antioxidant and anti-inflammatory functions of activated microglia have not yet been identified. Objectives: The present study aimed to investigate the anti-inflammatory and antioxidant role of OIS extract in a neuroinflammatory model of lipopolysaccharide (LPS)-stimulated microglia cells. Materials and Methods: BV2 microglial cells were treated with OIS extract in the presence or absence of LPS for 24 h. Subsequently, the levels of interleukin (IL)-6, nitric oxide (NO), and reactive oxygen species (ROS) were detected through enzyme-linked immunosorbent assay, Griess reagent, and the 2',7'-dichlorofluorescein diacetate fluorescent probe, respectively. In vitro antioxidant capacity was assessed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The total flavonoid and phenolic contents were also investigated. Results: OIS extract increased the levels of antioxidants detected by the DPPH and ABTS assays. The total flavonoid and phenolic content of OIS extract was 325.64 ± 4.95 and 50.47 ± 1.53 mg/g of dried extract, respectively. In addition, the levels of IL-6, NO, and ROS significantly decreased in LPS-induced BV2 microglia cells following treatment with OIS compared with the control. Conclusion: Taken together, the results of the present study demonstrated the antioxidant and anti-inflammatory properties of OIS in activated-BV2 cells. Thus, OIS extract may be used as a potential source of nutraceuticals for the development of health food supplements or as a novel anti-inflammatory herbal medicine.

Desenvolvimento de fitoterápicos a partir das folhas da nogueira-da-índia (Aleurites moluccanus): relato de experiência de parceria entre uma Universidade Comunitária e indústrias farmacêuticas nacionais

Este trabalho, de parcerias entre uma Universidade Comunitária e empresas farmacêuticas nacionais relata o desenvolvimento de novos e efetivos fitoterápicos obtidos a partir das folhas de Aleurites mollucanus (Euphorbiaceae), uma espécie exótica, proveniente da Ásia, adaptada no Brasil. Este projeto, embora ainda não tenha alcançado o estágio final de estudos clínicos e registro junto à ANVISA, representa uma experiência relevante a ser analisada à luz das dificuldades e superações no decorrer das etapas que compõem a cadeia de estabelecimento de um novo medicamento fitoterápico no Brasil. Com aprovação nas etapas de estudos não clínicos e na etapa clínica-fase I foram desenvolvidos, em escala piloto, comprimidos a base do extrato seco padronizado de A. moluccanus. Além disso, foram estabelecidas formulações como creme tópico e suspensão oral. A superação dos desafios para padronização do extrato em escala industrial, sob boas práticas de fabricação (BPF) e os aspectos de estabilidade das formulações, assim como a continuidade dos estudos, depende do cenário e consequente direcionamento do mercado. Este relato proporcionou uma visão sobre os percalços e as superações vivenciadas por pesquisadores de uma Universidade Comunitária brasileira, com foco na pesquisa e desenvolvimento de novo, efetivo e seguro fitoterápico analgésico e anti-inflamatório.

A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19.

Arisen in China, COVID-19 (SARS-CoV-II) is a novel coronavirus that has been expanding fast worldwide. Till now, no definite remedial drug or vaccine has been identified for COVID-19 treatment. Still, for a majority of infected patients, supportive therapy is the cornerstone of the management plan. To the importance of managing the COVID-19 pandemic, this article proposed to collecting capable medicinal plants and bioactive components in both treat and supportive therapy of this novel viral infection. Clinical points in the pathogenesis, symptoms, and complications of COVID-19 were considered. The effective plants and bioactives that may play a role in supportive therapy/management of COVID-19 were searched, collected through the "Scopus" database and listed in three sections. Numerous medicinal plants such as Citrus Spp., Camellia sinensis, and Glycyrrhiza glabra can interference with COVID-19 pathogenesis via inhibition of virus replication and entry to its host cells. Also, some anti-inflammatory herbal medicine such as Andrographis paniculata, Citrus spp., and Cuminum cyminum can relieve fever and cough in COVID-19 patients. Medicinal plants such as G. glabra, Thymus vulgaris, Allium sativum, Althea officinalis, and Panax ginseng may modulate the immune system and possess prevention and supportive therapy. However, more clinical data are required to confirm these hypotheses.

Network Pharmacology-Based Study on the Mechanism of Scutellariae Radix for Hepatocellular Carcinoma Treatment.

Hepatocellular carcinoma (HCC) is a malignant tumor without effective therapeutic drugs for most patients in advanced stages. Scutellariae Radix (SR) is a well-known anti-inflammatory and anticarcinogenic herbal medicine. However, the mechanism of SR against HCC remains to be clarified. In the present study, network pharmacology was utilized to characterize the mechanism of SR on HCC. The active components of SR and their targets were collected from the traditional Chinese medicine systems pharmacology database and the traditional Chinese medicine integrated database. HCC-related targets were acquired from the liver cancer databases OncoDB.HCC and Liverome. The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. Component-component target and protein-protein interaction networks were set up. A total of 143 components of SR were identified, and 37 of them were considered as candidate active components. Fifty targets corresponding to 29 components of SR were mapped with targets of HCC. Functional enrichment analysis indicated that SR exerted an antihepatocarcinoma effect by regulating pathways in cancer, hepatitis B, viral carcinogenesis, and PI3K-Akt signaling. The holistic approach of network pharmacology can provide novel insights into the mechanistic study and therapeutic drug development of SR for HCC treatment.

In Vitro and In Vivo Anti-Inflammatory Activities of Benjakul: A Potential Medicinal Product from Thai Traditional Medicine.

Benjakul (BJK) is a Thai traditional remedy consisting of five plants: Piper chaba Hunt., Piper sarmentosum Roxb., Piper interruptum Opiz., Plumbago indica Linn., and Zingiber officinale Roscoe. It is used as a first-line drug to balance patient's symptoms before other treatments. BJK ethanolic extract has been reported to show anti-inflammatory activity through various mediators, e.g., nitric oxide, TNF-α, IL-1β, and IL-6. Therefore, BJK could serve as a potential novel anti-inflammatory herbal medicine. However, studies on prostaglandin E2 (PGE2), one of the key mediators in acute inflammation, and anti-inflammation in animal models (in vivo) have not been done. This study investigated the anti-inflammatory activity of BJK extract and some of its chemical compounds against PGE2 production in murine macrophage (RAW 264.7) cell line and two in vivo models of anti-inflammatory studies. Ethanolic extract of BJK (BJK[E]) showed high inhibitory activity against PGE2 production with an IC50 value of 5.82 ± 0.10 μg/mL but its water extract (BJK[W]) was inactive. Two chemicals from BJK[E], i.e., plumbagin and myristicin, which served as biological markers, showed strong activity with IC50 values of 0.08 ± 0.01 and 1.80 ± 0.06 μg/mL, respectively. BJK[E] was administered both topically and orally to rats inhibited with inflammation induced by ethyl phenylpropiolate (rat ear edema model) and carrageenan (hind paw edema model). Moreover, the biological activity of BJK extract did not reduce after six-month storage under accelerated condition (40°C, 75% RH). This indicated its stability and a 24-month shelf-life under normal condition. These results supported not only the use of BJK in Thai traditional medicine but also the possibility of further development of phytopharmaceutical products from BJK.

Study on Anti-Inflammatory Effect and Major Anti-Inflammatory Components of PSORI-CM02 by Zebrafish Model.

PSORI-CM02 is an optimization formula of PSORI-CM01, which is a clinical herbal formula for the treatment for psoriasis in the Guangdong Provincial Hospital of Chinese Medicine. Previous research indicates that it plays a critical role in anti-inflammation and immunoregulation. Rhizoma smilacis glabrae (RSG) is one herbal medicine of PSORI-CM02, whose effective anti-inflammatory component is astilbin. This study aims to test the anti-inflammatory and immunoregulation effects of astilbin as well as RSG in PSORI-CM02, and we, respectively, used the CuSO4-induced neutrophil-specific transgenic zebrafish model Tg(mpx: EGFP) and the melanin allele mutated Albino strain zebrafish model to visualize the effects of neutrophil recruitment and macrophage phagocytosis. Our data indicated that both PSORI-CM02 and astilbin had anti-inflammatory effects, leading to a reduction in the recruitment of neutrophils and promotion in macrophage phagocytosis. Nevertheless, the negative liquor of Rhizoma smilacis glabrae (PSORI-CM02 without RSG) also had anti-inflammatory and promoting macrophage phagocytosis effects. The results revealed the formula excluding RSG also had anti-inflammatory and immunoregulation effects, which demonstrated that RSG was not the major anti-inflammatory herbal medicine in PSORI-CM02. Similarly, astilbin was not the major anti-inflammatory active ingredient in the formula. The anti-inflammatory and the promotion of macrophage phagocytosis effect of PSORI-CM02 in vivo zebrafish were the results of multiple component interaction, which was the common characteristic of the Chinese medicine compound.

Intracellular ROS Scavenging and Anti-Inflammatory Activities of Oroxylum indicum Kurz (L.) Extract in LPS plus IFN-γ-Activated RAW264.7 Macrophages.

Oroxylum indicum (L.) Kurz has been used as plant-based food and herbal medicine in many Asian countries. The aim of the present study was to examine the antioxidant and anti-inflammatory activities of O. indicum extract (O. indicum) in RAW264.7 cells activated by LPS plus IFN-γ. The phytochemical compounds in O. indicum were identified by GC-MS and LC-MS/MS. Five flavonoids (luteolin, apigenin, baicalein, oroxylin A, and quercetin) and 27 volatile compounds were found in O. indicum. O. indicum presented antioxidant activities, including reducing ability by FRAP assay and free radical scavenging activity by DPPH assay. Moreover, O. indicum also suppressed LPS plus IFN-γ-activated reactive oxygen species generation in RAW264.7 macrophages. It possessed the potent anti-inflammatory action through suppressing nitric oxide (NO) and IL-6 secretion, possibly due to its ability to scavenge intracellular ROS. The synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy results showed the alteration of signal intensity and integrated areas relating to lipid and protein of the activated RAW264.7 macrophages compared to unactivated cells. This is the first report of an application of the SR-FTIR technique to evaluate biomolecular changes in activated RAW264.7 cells. Our results indicate that O. indicum may be used as a potential source of nutraceutical for the development of health food supplement or a novel anti-inflammatory herbal medicine.

Src/NF-κB-Targeted Anti-Inflammatory Effects of Potentilla glabra var. Mandshurica (Maxim.) Hand.-Mazz. Ethanol Extract.

Inflammation is a complex protective response of body tissues to harmful stimuli. Acute inflammation can progress to chronic inflammation, which can lead to severe disease. Therefore, this research focuses on the development of anti-inflammatory drugs, and natural extracts have been explored as potential agents. No study has yet examined the inflammation-associated pharmacological activity of Potentilla glabra Var. mandshurica (Maxim.) Hand.-Mazz ethanol extract (Pg-EE). To examine the mechanisms by which Pg-EE exerts anti-inflammatory effects, we studied its activities in lipopolysaccharide (LPS)-treated murine macrophage RAW264.7 cells and an HCl/EtOH-induced gastritis model. LPS-triggered nitric oxide (NO) release and mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in RAW264.7 cells were suppressed by Pg-EE in a dose-dependent manner. Using a luciferase assay and western blot assay, we found that the NF-κB pathway was inhibited by Pg-EE, particularly by the decreased level of phosphorylated proteins of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunits (p65 and p50), inhibitor of kappa B alpha (IκBα), p85, and Src. Using an overexpression strategy, cellular thermal shift assay, and immunoprecipitation analysis, we determined that the anti-inflammatory effect of Pg-EE was mediated by the inhibition of Src. Pg-EE further showed anti-inflammatory effects in vivo in the HCl/EtOH-induced gastritis mouse model. In conclusion, Pg-EE exerts anti-inflammatory activities by targeting Src in the NF-κB pathway, and these results suggest that Pg-EE could be used as an anti-inflammatory herbal medicine.

Ranunculus bulumei Methanol Extract Exerts Anti-Inflammatory Activity by Targeting Src/Syk in NF-κB Signaling.

(1) Background: Ranunculus bulumei is a flowering plant that belongs to the Ranunculus species. Several Ranunculus species, such as R. aquatilis and R. muricatus, have traditionally been used to treat fever and rheumatism throughout Asia, suggesting that plants belonging to the Ranunculus species may have anti-inflammatory effects. To our knowledge, the pharmacological activity of R. bulumei has not been reported. Therefore, in this study, we aim to assess the anti-inflammatory activity of a methanol extract that was derived from R. bulumei (Rb-ME) in macrophage-mediated inflammatory responses and to identify the molecular mechanism that underlies any anti-inflammatory action. (2) Methods: The anti-inflammatory efficacy of Rb-ME was evaluated while using in vitro and in vivo experiments. The RAW264.7 cells and peritoneal macrophages were stimulated by lipopolysaccharide (LPS). In addition, LPS-induced peritonitis and HCl/EtOH-triggered gastritis models were produced. A nitric oxide (NO) assay, real-time PCR, luciferase reporter gene assay, western blot analysis, plasmid overexpression strategy, and in vitro kinase assay were used to determine the molecular mechanisms and target molecules of Rb-ME. The phytochemical active ingredients of Rb-ME were also identified by high performance liquid chromatograph (HPLC). (3) Results: Rb-ME reduced the production of NO and mRNA expression of iNOS, COX-2, IL-1β, and IL-6 without cytotoxicity. The protein secretion of TNF-α and IL-6 was also decreased by Rb-ME. HPLC analysis indicates that quercetin, luteolin, and kaempferol are the main active ingredients in the anti-inflammatory efficacy of Rb-ME. Rb-ME also blocked MyD88-induced NF-κB promoter activity and nuclear translocation of NF-κB subunits (p65 and p50). Moreover, Rb-ME reduced the phosphorylation of IκBα, Akt, p85, Src, and Syk, which are NF-κB upstream signaling molecules in LPS-activated RAW264.7 cells. According to the in vitro kinase assay, Rb-ME directly inhibits Syk kinase activity. The oral administration of Rb-ME alleviated inflammatory responses and the levels of p-IκBα in mice with LPS-induced peritonitis and HCl/EtOH-induced gastritis. (4) Conclusions Rb-ME has anti-inflammatory capacity by suppressing NF-κB signaling and it has been found to target Src and Syk in the NF-κB pathway. Based on this efficacy, Rb-ME could be developed as an anti-inflammatory herbal medicine.

Treatment of tonsillopharyngitis in children

Tonsillopharyngitis is a common disease among pediatric patients. Visits associated with sore throat account for 6 to 8% of all visits to pediatricians and general practitioners. Tonsillopharyngitis can have both infectious and non-infectious etiologies. In pediatric practice, most cases of upper respiratory tract infections are of viral origin, especially in children of early and preschool age. In most cases, uncomplicated course and non-infectious etiology of the disease do not require the administration of antibacterial drugs. The bacterial nature of the disease can be distinguished from the viral one using the data of culture analysis and rapid test for group A β-hemolytic streptococcus (GABHS) or Streptococcus pyogenes . The etiotropic therapy of streptococcal tonsillopharyngitis is antibiotic therapy. In GABHS, antibiotic therapy shortens the duration and reduces the severity of symptoms, reduces the Likelihood of purulent complications, post-streptococcal diseases and prevents the generalization of streptococcal infection. The use of modern antiseptic herbal medicines may be an additional and alternative line of therapy. The authors presented a literature review of the clinical trials results of a modern herbal medicine and provided the results of their own case of the combined treatment of a 10-year-old child with a diagnosis: acute moderate tonsillopharyngitis, bilateral cervical lymphadenitis; acute rhinitis; chronic adenoiditis, exacerbation; degree 2 adenoids. Antibacterial therapy included amoxicillin: oral: 100 mg/kg/day in 2 divided doses for 10 days, combined with an anti-inflammatory and antiseptic herbal medicine due to the complicated course of the disease in the form of concomitant regional lymphadenitis. The course of therapy resulted in clear positive changes: overall well-being improved as early as on the second day of treatment, sore throat and submandibular region ceased to cause pain by 5th day of treatment, the temperature became normal by 5th day of the disease. This clinical observation shows the possibility to introduce an anti-inflammatory herbal medicine to the complex treatment of acute tonsillopharyngitis in children, including cases of complicated course of the disease.

Modulation of LPS-induced inflammation in RAW264.7 murine cells by novel isoflavonoids from Millettia pulchra.

Millettia pulchra is a renowned anti-inflammatory herbal medicine in southeast provinces of China. However, the underlying anti-inflammation mechanism remained incompletely understood. Herein, four new isoflavones, pulvones A-D and eleven reported constituents were isolated from the stems of Millettia pulchra with their structures being elucidated by HRMS and NMR analysis. The anti-inflammatory activities of pulvones A and C were further evaluated due to the better inhibitory activity on nitric oxide production in LPS-stimulated RAW264.7 cells and no obvious cytotoxicity to RAW264.7 cells. Western blot showed that pulvones A significantly decreased the levels of iNOS and COX-2 proteins and pulvones C only decreased the level of iNOS protein. ELISA analysis demonstrated that pulvones A inhibited the production of both interleukin-6 (IL-6) and IL-1β while pulvones C showed better suppression effect on IL-1β production in LPS-stimulated RAW264.7 cells. Then, their potential inhibitory effects on NF-κB pathway were tested in LPS-stimulated RAW264.7 cells. Immunofluorescence and western blot assay showed that pulvones A and C reduced the nuclear translocation of NF-κB(p65) and interrupted IκB phosphorylation. The ADP-Glo™ kinase assay showed pulvones A and C could directedly inhibit the IKKβ kinase activity with the inhibitory rate of 40%, which were also verified by docking study. Collectively, these results suggested that pulvones A and C's anti-inflammatory effects were relevant to the interruption of NF-κB activation by inhibiting IKKβ kinase.