Strong Anti-inflammatory Activity Research Articles

Low dose of quercetin-loaded pectin/casein microparticles reduces the oxidative stress in arthritic rats

AimsQuercetin has been investigated as an agent to treat rheumatoid arthritis. At high doses it improves inflammation and the antioxidant status of arthritic rats, but it also exerts mitochondriotoxic and pro-oxidant activities. Beneficial effects of quercetin have not been found at low doses because of its chemical instability and low bioavailability. In the hope of overcoming these problems this study investigated the effects of long-term administration of quercetin-loaded pectin/casein microparticles on the oxidative status of liver and brain of rats with adjuvant-induced arthritis. Main methodsParticle morphology was viewed with transmission electron microscopy and the encapsulation efficiency was measured indirectly by X-ray diffraction. Quercetin microcapsules (10 mg/Kg) were orally administered to rats during 60 days. Inflammation indicators and oxidative stress markers were measured in addition to the respiratory activity and ROS production in isolated mitochondria. Key findingsQuercetin was efficiently encapsulated inside the polymeric matrix, forming a solid amorphous solution. The administration of quercetin microparticles to arthritic rats almost normalized protein carbonylation, lipid peroxidation, the levels of reactive oxygen species as well as the reduced glutathione content in both liver and brain. The paw edema in arthritic rats was not responsive, but the plasmatic activity of ALT and the mitochondrial respiration were not affected by quercetin, indicating absence of mitochondriotoxic or hepatotoxic actions. SignificanceQuercetin-loaded pectin/casein microcapsules orally administered at a low dose improve oxidative stress of arthritic rats without a strong anti-inflammatory activity. This supports the long-term use of quercetin as an antioxidant agent to treat rheumatoid arthritis.

A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis

Cathelicidin is a family of antimicrobial peptides (AMPs) existing in vertebrates, which play multiple functions in host responses against environmental stresses. All cathelicidins identified to date are cationic, no anionic member with net negative charges has been reported. In the present study, a novel anionic cathelicidin (TK-CATH) with a net charge of −3 was identified from the skin of the salamander, T. kweichowensis. Unlike most other cathelicidin members, it didn't exhibit direct antimicrobial activity. However, it demonstrated strong anti-inflammatory activity. It effectively inhibited the LPS-induced pro-inflammatory cytokine gene expression and protein production in amphibian leukocytes and mouse macrophages by inhibiting the LPS-activated mitogen-activated protein kinase (MAPK) signaling pathways. Besides, TK-CATH showed potent wound healing activity. It could effectively induce the production of several cytokines, chemokines and growth factors relating to wound healing, promote the motility and proliferation of keratinocytes, and accelerate the skin wound healing in a mouse full-thickness wound model. These results imply that TK-CATH participates in both the inflammatory phase and new tissue formation phase of wound repair process. Meanwhile, TK-CATH exhibited weak but effective free radical scavenging activity and low cytotoxicity. All the results above indicate that TK-CATH is a multifunctional peptide in the skin of the salamander T. kweichowensis. It may play important roles in host immune responses against bacterial infection and skin wound repair.

Glycogen-based pH and redox sensitive nanoparticles with ginsenoside Rh2 for effective treatment of ulcerative colitis

The purpose of this study is to construct a pH and redox sensitive nanoparticle to effectively deliver ginsenoside Rh2 for the treatment of ulcerative colitis (UC). Herein, glycogen was modified by urocanic acid and α-lipoic acid (α-LA) to obtain an amphiphilic polymer (LA-UaGly). Such polymer LA-UaGly could self-assemble to form nanoparticles (Blank NPs) in water with excellent stability, which could also successfully encapsulated ginsenoside Rh2 to form Rh2 nanoparticles (Rh2 NPs) with encapsulation efficiency of 74.36 ± 0.34%. DLS analysis indicated Rh2 NPs were spherical with a particle size of 128.9 ± 0.3 nm. As expected, Rh2 NPs exhibited typical pH and redox dual response release behaviour as well as the excellent in vivo safety. In vitro tests showed that Rh2 NPs could effectively internalize and release Rh2 into RAW264.7 cells, and protect cells from apoptosis (p < 0.05). More interestingly, Rh2 NPs exhibited strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6) (p < 0.05). In vivo experiments suggested that Rh2 NPs significantly ameliorated the weight loss, colon length, disease activity index (DAI) score, and myeloperoxidase (MPO) activity in mice caused by dextran sulfate sodium salt (DSS) (p < 0.05). Simultaneously, pathological analysis proved that Rh2 NPs could significantly reduce histological damage and inflammatory infiltration in mice. Rh2 NPs could also effectively regulate the intestinal flora of mice by improving the species uniformity and abundance of the intestinal flora of mice and restoring the species diversity of the intestinal flora. In addition, both in vivo and in vitro experiments proved that Rh2 NPs had stronger anti-inflammatory activity than Rh2. This study provides a promising strategy for the effective treatment of UC.

New Insights on Euphorbia dendroides L. (Euphorbiaceae): Polyphenol Profile and Biological Properties of Hydroalcoholic Extracts from Aerial Parts.

Euphorbia dendroides L. is a rounded shrub commonly found in the Mediterranean area well-known, since ancient times, for its traditional use. The aim of the present study was to investigate the phytochemical profile as well as the antioxidant and anti-inflammatory properties of flower (FE), leaf (LE), fruit (FrE), and branch (BE) hydroalcoholic extracts. For this purpose, a preliminary phytochemical screening followed by RP-LC-DAD-ESI-MS analysis, as well as several in vitro cell-free colorimetric assays, were carried out. Moreover, the toxicity of the extracts was investigated by the brine shrimp lethality assay. All extracts showed a high content of polyphenols, in particular phenolic acids (chlorogenic acid 0.74–13.80 g/100 g) and flavonoids (rutin 0.05–2.76 g/100 g and isovitexin 8.02 in BE). All the extracts showed strong and concentration-dependent antioxidant and anti-inflammatory activity with, on average, the following order of potency: FE, LE, FrE, and BE. Interestingly, all the extracts investigated did not show any toxicity on Artemia salina. Moreover, the only LD50 found (BE, 8.82 mg/mL) is well above the concentration range, which has been shown the biological properties. Considering this, this study offers the first evidence of the possible use of the polyphenol extracts from the aerial parts of E. dendroides as promising antioxidant and anti-inflammatory agents.

Surgical procedures in patients on aspirin. Literature Review

Aspirin is referred to as the original of the common non-steroid anti-inflammatory drugs and is used as a comparison measure to new ones. Aspirin, whose active ingredient is acetylsalicylic acid, combines strong antipyretic, analgesic, anti-inflammatory and anti-coagulant action. For the latter, aspirin is administered on an ongoing basis to patients for the prevention of cardiovascular events or recurrence of cerebral throm- bosis and therapeutically to patients with a history of heart attack or ischemic stroke. Taking aspirin as an anticoagulant chronic medication concerns dentists es- pecially when it comes to surgical procedures as it is likely to cause increased bleeding perioperatively. The management of the patient on aspirin varies depending on the reason aspirin is administered and its dosage, the co-administration of other antiplatelet or anticoagulant drugs and the severity of the surgical procedure itself. An interruption of antiplatelet medication is decided after assessing the above-mentioned criteria and con- sulting the patient’s physician. Additionally, in cases of increased bleeding risk like complex extractions, pre- prosthetic surgery, periodontal surgery, the procedure needs to be performed as atraumatically as possible and be accompanied by local haemostatic measures.

Saffron for “toning down” COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence

AimTo assess the potential role of saffron in downregulating inflammation and cytokine storm during COVID-19. Main findingsThree main compounds of saffron, i.e., crocetin esters, picrocrocin, and safranal, present strong antioxidant and anti-inflammatory action for several disease states (e.g., Alzheimer's, cancer, and depression) but have also been studied in COVID-19. In particular, based on our comprehensive review of both in vitro and in silico studies, saffron's essential oils and other constituents appear to have both immunomodulatory and anti-asthmatic actions; these actions can be particularly helpful to treat patients with respiratory symptoms due to COVID-19. Moreover, crocin appears to reduce the COVID-19-related cytokine cascade and downregulate angiotensin-converting enzyme 2 (ACE2) gene expression. Last, in silico studies suggest that saffron's astragalin and crocin could have inhibitory actions on SARS-CoV-2 protease and spike protein, respectively. ConclusionSaffron represents a promising substance for toning down cytokine storm during COVID-19, as well as a potential preventive treatment for COVID-19. However, appropriate randomized clinical trials, especially those using biomarkers as surrogates to assess inflammatory status, should be designed in order to assess the clinical efficacy of saffron and allow its use as an adjunct treatment modality, particularly in resource-poor settings where access to drugs may be limited.

Evaluation of the Organ Microscopy, Chemical Composition and Anti-inflammatory Potentials of Methanolic Leaf Extract and Fractions of Diaphananthe bidens

Aim: The study aims to investigate high-pressure liquid chromatographic (HPLC)-based chemical composition and anti-inflammatory activity of methanolic leaf extract and fractions of D. bidens.&#x0D; Study Design: The study is a laboratory-based research involving collection, identification and preparation, of plants, extraction, characterization and evaluation of the anti-inflammatory potential of D. bidens.&#x0D; Place and Duration of Study: Department of Pharmacognosy and Traditional Medicine, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria between January 2016 and June 2019.&#x0D; Methodology: Powdered leaves of D. bidens was macerated in methanol and the obtained crude extract was fractionated using n-hexane, ethylacetate, butanol, and water respectively. The acute toxicity profile of the extract was determined. Spectroscopic factors of the plant were assayed using HPLC-DAD and the anti-inflammatory activity of the extract and its fractions were evaluated.&#x0D; Results: Acute toxicity study showed that the crude extract has an LD50 &gt; 5,000 mg/kg. HPLC-DAD analysis revealed the presence of compounds including apigenin monoglycoside, quercetin 3-O-(6''O-acetyl) galactopyranoside, kaempferol 3-O-(6" O-malonyl) glucoside, genistein 8-C-glucoside, while anti-inflammatory study showed that the extract and fractions inhibited cellular activities of inflammatory mediators (86 – 97 %) in comparison with the diclofenac (53 %); thus, supporting its ethnomedicinal use in the treatment of inflammation.&#x0D; Conclusions: Methanolic extract of D. bidens has wide margin of safety. It has sufficient deposit of flavonoids which might be responsible for its strong anti-inflammatory activity that is comparable with diclofenac.

Wedelolactone alleviates acute pancreatitis and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis

Acute pancreatitis (AP) is an inflammatory disorder associated with multiple organ failure. Pyroptosis and ferroptosis are two newly recognized cell death, and whether pyroptosis and ferroptosis are involved in AP remain largely elusive. The nature compound Wedelolactone (Wed) exhibits strong anti-inflammatory and antioxidant activities, the present study aims to investigate the effect of Wed on AP and unravel whether Wed could protect against AP and relevant lung injury against pyroptosis and ferroptosis. Our results showed that the pyroptosis inhibitor disulfiram or ferroptosis inhibitor ferrostatin-1 significantly alleviated AP and associated lung injury in the taurocholate or caerulein-induced murine AP model. Administration with Wed ameliorated AP and lung injury as evidenced by improved pathological injuries, reduced serum pancreatic digestive enzymes, and proinflammatory cytokines. The in vivo and in vitro data demonstrated that Wed broadly inhibited caspase1/caspase11 activation, reduced mature interleukin-1β (IL-1β) and N-terminal domain of gasdermin D (GSDMD-N) level. The oxidative stress and lipid peroxidation were also suppressed along with the up-regulation of the ferroptosis antagonism marker glutathione peroxidase-4 (GPX4) in Wed treatment group. Wed promoted the transcriptional activity and the selenium sensitivity of GPX4. Moreover, the protective effects of Wed in caerulein-stimulated pancreatic acinar cells were markedly abrogated by the down-regulation of GPX4. Collectively, our data suggest that pyroptosis and ferroptosis play crucial roles in AP. Wed mitigated AP and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis.

Zanthoxylum alatum Roxb. seed extract ameliorates stress aggravated DSS-induced ulcerative colitis in mice: Plausible role on NF-κB signaling axis

Ethnopharmacological relevanceZanthoxylum alatum (ZA) Roxb (family: Rutaceae) plant has been traditionally used for multiple indications by local healers among different communities of South Asian countries mainly in India and Bangladesh. The extracts of ZA have reported strong anti-inflammatory and anti-oxidant activities, but no scientific report is available on its efficacy in intestinal inflammatory disorders like ulcerative colitis. Aim of the studyThe overall objective of our study was to evaluate the anti-inflammatory potency of hydro-ethanolic extract of Zanthoxylum alatum seed (ZAHA) using both in-vitro NF-κB-luciferase translocation assay and in-vivo stress aggravated dextran sodium sulfate (DSS)-induced ulcerative colitis model. Materials and methodsThe in-vitro anti-inflammatory effect of ZAHA extract was evaluated by luciferase assay in HEK293 cells. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in stress aggravated DSS-induced colitis model in C57BL/6 mice. Biochemical, histological and immunoblot analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. Characterization of the extract was done by LC-MS/MS study. ResultsInitial in vitro NF-κB-luciferase translocation assay showed that the hydroalcoholic extract of ZA (ZAHA) showed potent inhibitory activity for NF-κB translocation by TNF-α stimulation and hence this particular extract was further evaluated in stress aggravated DSS-induced ulcerative colitis model in C57BL/6 mice. Treatment of ZAHA for two weeks at a dose of 200 mg/kg significantly ameliorated the stress aggravated DSS-induced colitis in mice. Histological alterations, infiltration of inflammatory cells, and the levels of IL-1β, IL-6, TNF-α in colon tissue and serum samples were significantly decreased in ZAHA treatment groups compared to the stress aggravated DSS induced colitis animals. Moreover, the protein expressions of p-NF-κB, p-IκBα, p-STAT3, COX-2, and TNF-α were significantly reduced in colon tissues of ZAHA treated groups and also increased anti-oxidant markers like SOD-1, Nrf2 significantly when compared with disease control group. Characterization of the extract further by LC-MS/MS revealed the presence of several active compounds which could be responsible for its anti-inflammatory activity. ConclusionsThus from the above findings it can be concluded that ZAHA ameliorates stress aggravated DSS-induced ulcerative colitis due to its anti-inflammatory and anti-oxidant activity.

Phytochemical analysis using GC-FID, FPLC fingerprinting, antioxidant, antimicrobial, anti- inflammatory activities analysis of traditionally used Eucalyptus globulus essential oil

Eucalyptus globules is an widely distributed in tropical and subtropical regions. It has been widely used as folk medicine, and folk cosmetic owing to its antioxidant values. Despite its importance, phytochemical and pharmacological studies remain infancy. This study was aimed at extraction of essential oil by steam-distillation and evaluation of bioactive components, antioxidant, antimicrobial, anti-inflammatory activities along with analysis by UV-VIS, FT-IR and Fluorescent techniques. Fast protein liquid chromatography (FPLC) was used to confirm the presence of polyphenols. Different antioxidant activities like DPPH., ABTS.+, .OH, superoxide, nitric oxide and reducing power of the essential oil. Essential oil was analyzed by UV-VIS, FT-IR and Fluorescent techniques. In vitro antimicrobial activity was also monitored. FT-IR fingerprint qualitative analysis was performed using commercial standards. Considerable amount of flavonoids were detected in essential oil. Oil exhibited considerable scavenging activities of ABTS.+, .OH, superoxide, nitric oxide and reducing power. UV-VIS, FT-IR analysis revealed the presence of polyphenolics in essential oil. Fluorescent spectroscopy revealed the presence of fluorophores in essential oil. FPLC and FT-IR fingerprint analysis revealed the presence of bioactive constituents like rutin, tannic acid, vanillic acid and ascorbic acid in the essential oil. A strong anti-inflammatory activity of oil was observed using fluorescent spectroscopy. An appreciable in vitro antibacterial activity against gram-negative bacteria like Acetobacter aceti and Pseudomonas aeruginosa was detected. The data provides the scientific support to the use of essential oil from Eucalyptus globules as a potent herbal source of bioactive compounds possessing natural antioxidant activities in food and pharmaceutical industries.

Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model.

Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin’s effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.

Anti-Inflammatory Activity and Quality Control of Erysimum cheiri (L.) Crantz.

Wallflower (Erysimum cheiri) is employed as a popular herbal drug in traditional Persian medicine. Topical formulations including cerates, lotions, sitz baths, and poultices for inflammatory disorders such as arthritis, anal fissure, endometriosis, and mastitis are known. However, there is no monograph in current pharmacopoeia for the wallflower drug. The present study is aimed to screen in vitro anti-inflammatory activity of wallflower and perform quality control and characterization tests for different organs of the herb. In this regard, albumin denaturation activity, macroscopic and microscopic, phytochemical, HPTLC, and FT-IR characteristics were investigated. Wallflower showed strong anti-inflammatory activity compared to diclofenac sodium. The root (1.25, 2.5, and 5 mg/mL) and flower (10 mg/mL) extract exhibited higher anti-inflammatory activities than that of other plant organs at the same concentrations. Moreover, total ash was found higher in aerial parts (21.52 ± 0.06%) than flower (11.01 ± 0.03%), root (5.03 ± 0.03%), and seed (6.95 ± 0.06%), while water-soluble ash was higher in seed (34.89 ± 0.26%) than flower (5.00 ± 0.03%), aerial parts (7.16 ± 0.06%), and root (5.04 ± 0.01%). Acid-insoluble ash and sulphated ash were higher in root (9.50 ± 0.04%) and aerial part (28.37 ± 0.57%), respectively. In addition, loss on drying was ranged from 2.20 ± 0.20% in flowers to 6.00 ± 0.10% in aerial parts. On the other hand, HPTLC analysis verified cardenolide compounds in all organs of the herb, and quercetin was detected in the flavonoid fingerprint of acid hydrolysed flowers. According to FT-IR results, the observed spectral region at ~3500 cm−1 attributed to -OH stretching vibration. Also, C–H (~2900-2950 cm−1), isothiocyanate (~2340 cm−1), -C=O (~1740 cm−1), conjugated C=C of the aromatic ring (~1650 cm−1), and structure of the aromatic group (~1200-1000 cm−1) were monitored. This work is the first study to the best of our knowledge, suggesting wallflower as a potential drug candidate with the basis for a monograph in addition to initial in vitro anti-inflammatory data.

English

Rheum emodi Wall. ex Meissn is a popular medicinal herb having wide application in traditional medicine for treating of several diseases. The present study was aimed to identify and isolate phytochemicals present in ethyl acetate extract fraction of R. emodi and to evaluate the anticancer and anti-inflammatory activities of water/organic solvent fractions and isolated compounds of R. emodi rhizome extracts. Based on the structure, flavonoid compound i.e., Myricitrin (sym. Myricetin 3- rhamnoside), myricetin 3-galloylrhamnoside and myricetin were identified to be present in ethyl acetate extract. The molecular weight of compound 1 cannot be identified; while compound 5 remained unknown as there was not enough evidence to propose its structure. The isolated compounds and different solvent fractions were tested for their anticancer and antiinflammatory activities. Among Myricetins derivatives, particularly unknown compounds significantly induced the apoptosis and restrained the proliferation of cancer cell lines (A549 and MCF-7) and inhibited the LPS induced NO production (proinflammatory mediator), IL-6 activity, IL-1β and TNF-α (cytokines) activity in RAW 264.7 macrophages in a dose dependent manner and was effective even at lower concentration (50 µg/mL). Similarly, the higher concentration of aqueous and solvent fractions exhibited strong cytotoxic and anti-inflammatory activities. However, water and dichloromethane fractions were most effective in inhibiting the anticancer activities in A549 and MCF-7 cancer cell lines, respectively. At lower concentration (50 and 100 µg/mL), highest inhibition activity for NO, IL-6 and IL-1β was noted with ethyl acetate fractions and n-Hexane fractions; while water and n-Butanol (fractions) strongly inhibited the TNF-α activity at lower (100 µg/mL) and high (200 µg/mL) concentration, respectively. In conclusion, the isolated compounds from R. emodi rhizome extracts and its rhizome solvent fractions exhibit strong anti-cancer and anti-inflammatory activities and can be used to develop chemotherapeutics and anti-inflammation drugs. © 2021 Friends Science Publishers

Lipase-catalyzed selective esterification of catechin

Catechins show strong antioxidant, antitumoral, antiviral, and anti-inflammatory activities. The uses of catechins in food, cosmetic, and pharmaceutical formulations seem very attractive. Unfortunately, solubility and stability of catechins are poor in apolar media, which limits their efficient uses. In order to improve the solubility of catechins in the oil phase and maintain their oxidation resistance, a regioselective enzymatic acylation was investigated. The effects of reaction medium, water content, carbon chain length of acyl donor and other factors on the acylation reaction were studied, catechins were enzymatically esterified with an aliphatic acid (stearic acid) using an immobilized lipase Novozym 435 in n-butanol. The results show that when the ratio between catechins and stearic acid was 1:5, adding molecular sieves 4A after 11 h of reaction and the temperature of 60 °C led to the maximum conversion yield of 60.36%. Studies have shown that catechin stearate has a higher antioxidant activity than vitamin E and dibutyl hydroxytoluene (BHT).

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

Christensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.

Potential of phytomedicine in the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease caused by an abnormal response of the intestinal mucosal immune system, including ulcerative colitis and Crohn's disease. IBD is also accompanied by extraintestinal complications, such as joint, skin, and eye diseases. In recent years, phytomedicine has played an important role in the treatment of IBD because of its strong anti-inflammatory activities and minor side effects. Due to the lack of a review of the literature examining the extent to which phytomedicine can be used to treat IBD, this paper summarizes the experimental research on IBD from the perspective of phytomedicine according to the structural classification of phytomedicine and provides a reference for the further development of new IBD therapies.

Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism.

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.

Immunomodulatory Activity of Electrospun Polyhydroxyalkanoate Fiber Scaffolds Incorporating Olive Leaf Extract

Olive tree is a well-known source of polyphenols. We prepared an olive leaf extract (OLE) and characterized it via high performance liquid chromatography (HPLC) analysis. OLE was blended with different polyhydroxyalkanoates (PHAs), namely, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) and polyhydroxybutyrate/poly(hydroxyoctanoate-co-hydroxydecanoate) (PHB/PHOHD), to produce fiber meshes via electrospinning: OLE/PHBV and OLE/ (PHB/PHOHD), respectively. An 80–90% (w/w%) release of the main polyphenols from the OLE/PHA fibers occurred in 24 h, with a burst release in the first 30 min. OLE and the produced fiber meshes were assayed using human dermal keratinocytes (HaCaT cells) to evaluate the expression of a panel of cytokines involved in the inflammatory process and innate immune response, such as the antimicrobial peptide human beta defensin 2 (HBD-2). Fibers containing OLE were able to decrease the expression of the pro-inflammatory cytokines at 6 h up to 24 h. All the PHA fibers allowed an early downregulation of the pro-inflammatory cytokines in 6 h, which is suggestive of a strong anti-inflammatory activity exerted by PHA fibers. Differently from pure OLE, PHB/PHOHD fibers (both with and without OLE) upregulated the expression of HBD-2. Our results showed that PHA fiber meshes are suitable in decreasing pro-inflammatory cytokines and the incorporation of OLE may enable indirect antibacterial properties, which is essential in wound healing and tissue regeneration.

Rapid identification, isolation, and evaluation on anti-neuroinflammatory activity of limonoids derivatives from the root bark of Dictamnus dasycarpus

A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as “Baixianpi” in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC50 value of 1.8 μM. Nuclear Factor kappa B (NF-κB) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), interleukin 6 (IL-6) via inactivating NF-κB signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-κB signaling pathways.

Commensal flora triggered target anti-inflammation of alginate-curcumin micelle for ulcerative colitis treatment

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by dysregulation of colon immune response. Curcumin (Cur) has strong anti-inflammatory activities, but the application is severely hindered by the extremely hydrophobicity and pitiful bioavailability. Alginate (Alg), a natural polysaccharide with ideal solubility and biosafety, was introduced to prepare the esterified alginate-curcumin conjugate (Alg-Cur) and constructed stable Alg-Cur micelle in physiological solutions. Compared with crystalline Cur, the target anti-inflammatory activities of Alg-Cur were systematically investigated. The results showed that Alg-Cur exerted effective anti-inflammatory effects in Raw 264.7 cells. After oral administration, 92.32 % of Alg-Cur reached colon, and the ester bonds were quickly sheared by abundant esterase produced by commensal anaerobic flora. The released Cur was quickly absorbed in-situ in monomolecular state, and effectively ameliorated the colonic inflammation and tissue damage by inhibiting the TLR4 expression in colonic epithelial cell, reducing the transcription and expression of the pro-inflammation cytokines downstream, as well as the infiltration of lymphocytes, macrophages and neutrophils. The Alg-Cur micelle effectively enhanced the hydrophilicity and bioavailability of Cur, and the commensal flora triggered Cur release showed great potential for UC treatment.