Clinical efficacy of intense pulsed light combined with low-dose intralesional corticosteroids in treating noninfectious granulomas after mesotherapy: A case series analysis.

BACKGROUND: Mesotherapy is a popular cosmetic procedure for localized delivery of substances. However, due to the lack of standardized processes, there are potential risks of adverse reactions. Granulomas formation is one of the chronic reactions which impose significant physical and mental burdens on patients. OBJECTIVES: The aim of this analysis is to evaluate the safety and feasibility of combining intense pulsed light (IPL) with intralesional corticosteroids for treating noninfectious granulomas after mesotherapy. METHODS: This retrospective observational case series included patients who suffer from noninfectious granulomas after mesotherapy and received combination of IPL and intralesional corticosteroids treatment between October 2021 and December 2022 at Peking University Shenzhen Hospital, Shenzhen, China. The process and effect were analyzed and summarized. RESULTS: Among the seven patients, five expressed extreme satisfaction with the efficacy, while two was slightly satisfied. The physicians believed that all patients had shown significant improvement. No adverse reactions or recurrences were observed during follow-up. CONCLUSION: Based on this analysis, the application of the combined treatment in patients suffering from noninfectious granuloma due to mesotherapy demonstrates good clinical efficacy and safety, making it worth considering as a treatment option.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms.

Adjunctive Intravitreal Anti-vascular Endothelial Growth Factor and Moxifloxacin Therapy in Management of Intraocular Tubercular Granulomas.

PURPOSE: To report pre and post treatment levels of VEGF-A in the aqueous humour of patients with intraocular tubercular granulomas and study the effect of a combined intravitreal anti-VEGF bevacizumab and moxifloxacin therapy on their regression. METHODS: Aqueous samples of 10 consecutive patients with intraocular tubercular granulomas obtained before and after initiating treatment were subjected to ELISA for analysing intraocular VEGF-A levels. Intravitreal injections of bevacizumab and moxifloxacin were given weekly till complete regression of these granulomas. All patients received the usual four-drug ATT and oral corticosteroids. RESULTS: Mean baseline VEGF-A level was 1004.27±411.40 pg/ml (401.32-1688.95) that reduced significantly to 27.62±46.86 pg/ml (6.9-131.83) at the last injection. Meannumber of intravitreal injections was 3.1 (2-4). We found significant correlation of decreasing levels of aqueous VEGF-A with the clinical regression of these tubercular granulomas. CONCLUSIONS: Intraocular TB granulomas have high levels of VEGF-A. Weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin as an adjunct to the standard care may cause prompt regression of tubercular granulomas. ABBREVIATIONS: TB: Tuberculosis; IOTB: Intraocular tuberculosis; VEGF: Vascular endothelial growth factor; RD: Retinal detachment; Mtb: Mycobacterium tuberculosis; ATT: Antitubercular therapy; AMD: Age-related macular degeneration; SRF: Subretinal fluid; ELISA: Enzyme immunosorbent assay; PCR: Polymerase chain reaction; ONH: Optic nerve head; MDR-TB: Multidrug-resistant tuberculosis; pg/ml: picogram/milliliter; ESR: Erythrocyte sedimentation rate; CECT: Contrast enhanced computed tomography; DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; BSL: Biosafety level; BCVA: Best corrected visual acuity; HM: Hand movements; KP: Keratic precipitates; PSC: Posterior subcapsular cataract; PS: Posterior synechiae; CRA: Chorio-retinal atrophy; IVMP: Intravenous methyl prednisolone; OCT: Optical coherence tomography; RPE: Retinal pigment epithelium; FFA: Fundus fluorescein angiography; ICG: Indocyanine angiography; RAP: Retinal arterial proliferans.

In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. AIM OF THE STUDY: The objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. MATERIALS AND METHODS: To study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. RESULTS: The topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. CONCLUSIONS: The current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

Potentiality of curcumin on ISHAK scoring system and the expressions of BAX, IL-17A, and EGF in the treatment ofSchistosoma mansoni infection using Swiss albino mice.

The present study evaluated the antiparasitic effect of curcumin extract on Schistosoma mansoni in Swiss albino mice. The experimental design included four groups of S. mansoni - infected mice; without treatment (controls), curcumin-treated, Praziquantel (PZQ)-treated, and PZQ +curcumin treated mice. The results showed that curcumin improved ISHAK confluent necrosis score up to zero. PZQ +curcumin showed a significant reduction in portal inflammation. Both activity and fibrosis demonstrated lower scores in all treated groups, however, PZQ revealed a marked increase in confluent necrosis and interface hepatitis. Besides, the lobular inflammation revealed worsening in the overall ISHAK score in all treated groups compared with the control. Few periocular granulomas were recovered by PZQ +curcumin treatment at day 35 post-treatment (6±1.2), P-value <0.05. Curcumin revealed a mild reduction (60±7.376). Curcumin-treated groups, with and without PZQ, resulted in higher significant Immunoreactivity score (IRS) for Bcl-2-associated X (BAX) and lower Interleukine- 17A (IL-17A), and Human epidermal growth factor (EGF), compared to the control. However, PZQ revealed a lower mean IRS value in BAX, higher IL-17A and EGF in the periovulatory granuloma. It was concluded that PZQ +curcumin treatment had a potent synergistic outcome through lessening the number of granulomas, the inflammatory events, and the expression of EGF, and amelioration of apoptosis in the periovulatory granulomas if compared with either PZQ or curcumin alone.

Dandelion (Taraxacum officinale) Improves the Therapeutic Efficiency of Praziquantel in Experimental Schistosomiasis.

PURPOSE: Although praziquantel (PZQ) has a wide use as an anti-schistosome agent, many of its imperfections and side effects have been reported in many studies. The current study aims to evaluate the curative effect of a natural dandelion extract (Taraxacum officinale) on schistosomiasis either alone or in combination with PZQ based on parasitological, immunological, histopathological and molecular investigations. METHODS: Mice were experimentally infected with Schistosoma mansoni cercariae and then divided into four groups, Schistosoma spp.-infected untreated group (IC group), Schistosoma spp.-infected group of mice treated with dandelion (I-Dn group), Schistosoma spp.-infected group of mice treated with PZQ (I-PZQ group), and Schistosoma spp.-infected group of mice treated with both PZQ and dandelion (I-PZQ + Dn group). Treatment started 45 days' post-infection. Besides, non-infected, non-treated mice served as the negative healthy control group (HC group). RESULTS: The present results indicated that dandelion administration significantly reduced the worm burden, ova number, and the number and diameter of hepatic granulomas as compared to the untreated infected group. The results also showed that the levels of IL-6 and TNF-α were significantly decreased in the combined treatment group (I-PZQ + Dn) as compared to the I-PZQ group. Administration of dandelion-only remarkably reduced AST and ALT activities associated with schistosomiasis. Moreover, hepatic DNA damage assessed by comet assay was significantly inhibited in the combined treated group compared to the infected untreated and PZQ treated groups. CONCLUSION: The results concluded that combined treatment of PZQ and dandelion extract improved immune response, decreased the number and diameter of granulomas, and inhibited DNA damage, indicating a reduction in liver fibrosis associated with schistosomiasis. The present study focused on the potential effect of dandelion as an adjunct medication for therapeutic properties of PZQ.

The potent effect of silymarin combination with Praziquantel or mirazid for Schistosoma mansoni treatment in infected male swiss albino mice.

This work was carried out to investigate the effect of silymarin combination in the therapeutic plane of schistosomiasis with praziquantel or mirazid to enhance the liver and reduce fibrosis. Mice were divided into 2 main groups, the 1st uninfected group served as control and the 2nd group infected subcutaneously with 60 cercaria of S. mansoni per each. The infected group was subdivided into 5 subgroups, the 1st kept untreated, the 2nd and 3rd treated at the 7th week of infection with (600 mg/kg) of PZQ orally for 3 consecutive days, while the 3rd treated also orally with (150 mg/kg) of silymarin daily for 11 weeks. The 4th and 5th groups treated orally at the 7th week of infection with 600 mg/kg of MZ for 3 consecutive days, while the 5th group treated orally also with 150 mg/kg of silymarin daily for 11weeks. IgG determination showed high level in the untreated infected group. Furthermore, the infected groups treated with PZQ and PZQ with silymarin displayed the lower levels than treated with MZ. Additionally, the untreated infected group showed severe pathological changes as hyaline degeneration, inflammation, presence of worm burdens in dilated portal veins, granulomas as well as depositions of collagenous and reticular fibers indicated intense fibrosis. Treatment with PZQ alone resulted in reduction of pathological signs and decreasing of granulomas. Combination with silymarin to PZQ therapy revealed more improvement for liver besides to lowering of granulomas areas and volumes and decreasing of fibrosis. Whereas, treatment with MZ was less effective than PZQ to reduce granulomas areas, volumes and fibrosis. Although, combination of silymarin to MZ treatment resulted in more curative signs and reduction of granulomas areas, volumes and fibrosis. Furthermore, the present study concluded that PZQ still the more effective drug of schistosomiasis treatment than MZ. The silymarin is very useful in schistosomiasis treatment when combined with PZQ or MZ due to its anti-fibrotic effect.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Ficus vogelii methanol leaf extract ameliorates inflammation and arthritis by modulating osmotic fragility in C57BL/6J mice.

The study evaluated the membrane-stabilizing potentials in red blood cells and anti-inflammatory properties in C57BL/6J mice of the methanol leaf extract of Ficus vogelii. Animals were treated orally with different doses of the extract (50, 100, 200 mg/kg) for 30 days and their blood was measured for membrane stability at different saline concentrations. Diclofenac (12.5 mg/kg) or Indomethacin (10 mg/kg) was used as standard in the anti-inflammatory studies. The mean corpuscular fragility (MCF) values and their corresponding percentage stabilization increased significantly (p≤0.05) in the treatment groups compared to the negative control. Treatment of mice with 50, 100 and 200 mg/kg of the extract significantly (p≤0.05) inhibited carrageenan-induced paw oedema in mice. The highest dose (200 mg/kg) showed lower anti-inflammatory activity compared to Diclofenac (12.5 mg/kg). Daily administration of the extract significantly (p≤0.05) suppressed adjuvant-induced paw arthritis by day 15 and 30 post arthritis induction. Ficus vogelii extract inhibited granuloma formation significantly. The anti-inflammatory effects of methanol leaf extract of Ficus vogelii on granuloma formation were comparable to that of Indomethacin (10 mg/kg). In summary, this study showed that the methanol leaf extract of Ficus vogelii possessed membrane-stabilizing potentials and anti-inflammatory properties, therefore, providing further proof that the leaves contain an active compound with potent anti-inflammatory activity.

Trigonella foenum-graecum Seeds Oil Attenuated Inflammation and Angiogenesis in vivo through Down-Regulation of TNF-α.

INTRODUCTION: Inflammation is a vital reaction of the natural immune system that protects against encroaching agents. However, uncontrolled inflammation can lead to complications. Trigonella foenumgraecum is traditionally used as an anti-inflammatory herb. OBJECTIVES: The current study was conducted to explore the antioxidant, anti-inflammatory, and antiangiogenic potentials of Trigonella foenum-graecum seeds oil. METHODS: Oil was extracted from seeds of Trigonella foenum-graecum by cold press method and labelled as TgSO. Phytochemical (GC-MS, Folin-Ciocalteu method) and metal analyses were conducted to evaluate the metalo-chemical profile of TgSO. In vitro antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis-3- ethylbenzothiazoline-6-sulfonic acid and ferric reducing antioxidant power) were performed to assess its antioxidant potential. In vitro antimicrobial activity was evaluated using agar disc diffusion method and the safety profile of TgSO was assessed in acute toxicological studies following OECD 425 guidelines. In vivo antiinflammatory activities of TgSO were assessed in carrageenan, serotonin, histamine, formalin, and cotton pelletinduced oedema models. Serum TNF-α, Superoxide Dismutase (SOD) and, Catalases (CAT) levels were assessed by ELISA kits. In vivo antiangiogenic activity of TgSO was screened in chick Chorioallantoic Membrane (CAM) assay. Histopathological studies using excised paws were conducted to observe the effects of TgSO treatment at the tissue level. In silico docking studies were conducted to screen the binding potentials of identified compounds with TNF-α. RESULTS: Extraction by cold press method yielded 16% of TgSO. Phytochemical analysis of TgSO through GCMS showed the presence of eugenol, dihydrocoumairn, heptadecanoic acid, tri- and tetradecanoic acid, and hexadecanoic acid, respectively. Total phenolic contents of TgSO were found to be 0.30±0.01mg/g gallic acid equivalent in Folin-Ciocalteu method. Metal analysis indicated the presence of different metals in TgSO. Findings of antioxidant models showed the moderate antioxidant potential of TgSO. Findings of antimicrobial assays showed that TgSO was active against bacterial (S. aureus, S. epidermidis) and fungal (C. albicans, and A. niger) strains. In vivo toxicity study data showed that TgSO was safe up to the dose of 5000 mg/kg. Data of oedema models showed a significant (p<0.05) reduction in oedema development in TgSO treated animals in both acute and chronic models. Histopathological evaluations of paws showed minimum tissue infiltration with inflammatory cells in TgSO-treated animals. Treatment with TgSO also significantly (p<0.05) down-regulated TNF-α in serum while levels of SOD and CAT were up-regulated. Findings of the CAM assay revealed the antiangiogenic activity of TgSO. Findings of in silico docking studies showed that identified phytoconstituents can bind with culprit cytokine (TNF-α). CONCLUSION: Data obtained from the current study conclude that TgSO has antioxidant, anti-inflammatory, and antiangiogenic effects that validate its traditional uses. Synergistic actions of different phytoconstituents are proposed to be responsible for the observed effects.

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica.

BACKGROUND: Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma japonicum infection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweed Fucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. METHODS: We evaluated the hepatic pathology from S. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in the S. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detected in vitro. Furthermore, macrophages were treated with fucoidan in vitro and to detect the inflammatory cytokines. RESULTS: Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response during S. japonicum infection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treated S. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treated S. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-ß were dramatically increased in the livers from S. japonicum-infected mice after fucoidan treatment. Furthermore, in vitro stimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. CONCLUSIONS: These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress of S. japonicum infection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.

Majocchi's granuloma on the forearm caused by Trichophyton tonsurans in an immunocompetent patient.

Majocchi's granuloma is an uncommon fungal infection of the dermis and subcutaneous tissue. The most frequently identified cause of Majocchi's granuloma is anthropophilic Trichophyton rubrum, and it is most commonly located on the anterior aspect of the lower limbs in women. Here, we report a case of Majocchi's granuloma on the forearm, a site that is rarely involved, in a 62-year-old woman who had been bitten by a dog. Histological examination revealed a dense dermal infiltrate composed of lymphoplasmacytic cells and neutrophils, with hyphae in the dermis. The presence of the fungus, Trichophyton tonsurans, was confirmed by mycological examination and molecular methods. Therefore, histological and mycological examination confirmed the diagnosis of Majocchi's granuloma. The patient was treated with local moxibustion and itraconazole, 200 mg/day, for 60 days, which facilitated a complete resolution of the lesions.

Anti-Inflammation Effect of Small Molecule Oligopeptides Prepared from Panax ginseng C. A. Meyer in Rats.

The present study was designed to investigate the anti-inflammatory effects of ginseng oligopeptides (GOPs). For the anti-inflammatory activity, dextran-induced paw edema and granuloma models were used in Sprague-Dawley rats (180⁻200 g, 12 weeks old, n = 10). Rats were treated orally with GOPs (0, 62.5, 125, 250 and 500 mg/kg) for prophylaxis. In the granuloma model, the levels of NO, Tumor necrosis factor-α (TNF-α), interleukin IL-ß, and interleukin IL-10 in serum were evaluated. In addition, in the edema model, the level of TNF-α, prostaglandin E2 (PGE2), Leukotriene D4 (LTD4), and the platelet activating factor (RAF) in paw tissue were detected. PCR assessed the effect of GOPs on the expression of MAPK and NF-κB. The results showed that oral administration of GOPs inhibited inflammation caused by cotton pellet and dextran. GOPs significantly inhibited the edema formation via MAPK and NF-κB. These findings suggested that GOPs have a beneficial effect on acute and chronic inflammation, and the mechanism possibly mediated by inhibiting gene expression involved in inflammation and downregulating inflammatory mediators.

Anti-inflammatory and analgesic activity based on polymorphism of cedrol in mice.

Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.

Humanized Mouse Model Mimicking Pathology of Human Tuberculosis for in vivo Evaluation of Drug Regimens.

Human immune system mice are highly valuable for in vivo dissection of human immune responses. Although they were employed for analyzing tuberculosis (TB) disease, there is little data on the spatial organization and cellular composition of human immune cells in TB granuloma pathology in this model. We demonstrate that human immune system mice, generated by transplanted human fetal liver derived hematopoietic stem cells develop a continuum of pulmonary lesions upon Mycobacterium tuberculosis aerosol infection. In particular, caseous necrotic granulomas, which contribute to prolonged TB treatment time, developed, and had cellular phenotypic spatial-organization similar to TB patients. By comparing two recommended drug regimens, we confirmed observations made in clinical settings: Adding Moxifloxacin to a classical chemotherapy regimen had no beneficial effects on bacterial eradication. We consider this model instrumental for deeper understanding of human specific features of TB pathogenesis and of particular value for the pre-clinical drug development pipeline.

Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir.: Chemical characterization, anti-nociceptive and anti-inflammatory activities of methanol extract of leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Sphenodesme involucrata var. paniculata (C. B. Clarke) Munir is native as well as endemic to South India. Its leaves are used in folklore medicine to treat pain and rheumatism. OBJECTIVE: This study was aimed to investigate the chemical characterization, anti-nociceptive and mode of action underlying the anti-inflammatory effects of methanol extract of S. involucrata leaves (MESi). METHODS: Phytoconstituents of MESi was analyzed using colorimetric and liquid chromatography-mass spectrometry (LC-MS) methods, and the oral acute toxicity was evaluated in mice up to 2000 mg/kg. The anti-nociceptive effect was evaluated in hot plate and writhing tests; whereas the anti-inflammatory effect was investigated using carrageenan, cotton pellet and lipopolysaccharide (LPS)-induced peritonitis models at doses of 100, 200 and 400 mg/kg. Additionally nitric oxide (NO) and inflammatory cytokines levels were also evaluated. RESULTS: MESi exhibited the high content of phenolics and flavonoids as well as compounds like austricine, benzylglucosinolate, gossypin, justicidin B and cirsimarin were detected in LC-MS. In the acute toxicity study, oral administration of MESi did not cause any toxic effect and mortality up to 2000 mg/kg body weight in mice. In the anti-nociceptive tests, MESi augmented the latency period at higher dose (400 mg/kg), on the other hand attenuated writhings at the dose of 400 mg/kg by 87.87% (p < 0.001). In the carrageenan induced paw oedema MESi significantly inhibited the oedema formation at dose 400 mg/kg by 32.1%; besides, anti-inflammatory effect was registered in the cotton pellets-induced inflammation model at doses 200 and 400 mg/kg by 27.09% (p < 0.001) and 35.47% (p < 0.001) respectively. On the other hand, MESi appreciably reduced leukocyte, neutrophils infiltration, nitric oxide, TNF-α and IL-1ß levels and increased the IL-10 level in the (LPS)-induced peritonitis model. CONCLUSION: The results conclude that MESi has no acute toxic effect and it demonstrated potent anti-nociceptive and anti-inflammatory activities. Its anti-nociceptive activities are probably mediated through peripheral and central mechanisms. The anti-inflammatory effect of MESi involved the inhibition of neutrophils migration and the modulation of Th1 and Th2 cytokines, besides the attenuation of production of PGE2 and NO. LC-MS analysis revealed the predominant presence of the austricine, benzylglucosinolate, gossypin, justicidin B and cirsimarin compounds, which are possibly involved in the anti-nociceptive and anti-inflammatory effects of MESi. The current study provided supportive evidence for the folklore use of S. involucrata in the treatment of pain and inflammatory conditions.

Polysaccharides from Citrus grandis associate with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophages.

Chronic pharyngitis is characterized as a common inflammation of the pharyngeal mucosa, and anti-inflammatory medications are the common treatment to relieve it. Polysacharides of Citrus grandis L. Osbeck (PCG) and luteolin have been reported to have anti-inflammatory activities. In this study, the protective effects of PCG and luteolin on chronic pharyngitis are evaluated and the underlying mechanisms are explored. PCG and luteolin are administrated to animal models with granuloma, ear edema and chronic pharyngitis and the effects of PCG and luteolin on disease severity are evaluated. We also evaluate the effects of PCG and luteolin on inflammatory cytokine production in macrophages stimulated with lipopolysaccharides (LPS)/interferon-gamma (IFN-γ) and detect the effects of PCG and luteolin on macrophage polarization. Finally, we evaluate the effects of PCG and luteolin on activations of LPS-induced downstream signaling pathways. PCG and luteolin alleviate the disease severity of granuloma, ear edema and chronic pharyngitis. PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage.

Anti-allergy and anti-tussive activity of Clitoria ternatea L. in experimental animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower. AIM OF THE STUDY: Ethanolic extract of Clitoria ternatea flowers (ECT) was evaluated for its anti-allergy and anti-tussive potential in experimental animals. Additionally, the anti-inflammatory potential of ECT was carried out to draw a plausible mechanism of action of the drug. MATERIALS AND METHODS: In-vitro anti-asthmatic activity of ECT was evaluated in goat tracheal chain and isolated guinea pig ileum preparations. Acute and chronic anti-asthmatic activity of ECT (100, 200 and 400 mg/kg; p.o.) was estimated in histamine aerosol exposed guinea pigs and in OVA sensitized and challenged mice respectively. Anti-tussive activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against sulfur dioxide- and citric acid-induced cough in experimental animals. Moreover, the anti-inflammatory activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against carrageenan- and acetic acid-induced inflammation in rats. RESULTS: ECT attenuated histamine-induced contraction in both goat tracheal chain and isolated guinea pig ileum preparations. ECT (400 mg/kg) attenuated histamine-induced dyspnoea and OVA-induced changes in differential cell count in broncheoalveolar fluid, levels of interleukins (IL-1beta and IL-6) and immunoglobulin (OVA-sensitive IgG1) in animals. ECT (400 mg/kg) further ameliorated sulfur dioxide- and citric acid-induced cough in experimental animals. Additionally, ECT (400 mg/kg) attenuated inflammation in carrageenan and acetic acid challenged rodents. CONCLUSIONS: Standardized ECT could be considered as a potential therapeutic alternative in the management of allergy-induced asthma.