Bronco T (Shirisadi kasaya), a polyherbal formulation ameliorates LPS induced septicemia in rats

Septicemia is a life-threatening state, leading to multi-organ failure, ARDS and death. So, efforts are being made to identify novel therapies. Here, Bronco T (BT), a polyherbal formulation developed in 1984 for treating asthma, has been repurposed against septicemia induced ALI. The LPS (3mg/kg BW) was injected intraperitoneally before 24 hours, of surgery to assess the cardiorespiratory parameters, blood PaO2/FiO2, pulmonary water content and histological changes in the lungs. The pentoxifylline (PTX) (25 mg/kg b.w.) was used as the positive control. The PTX was given one hour before LPS and BT was given 3 hours (orally in different doses of 3, 1.5 and 0.75 gm/kg BW) to maintain the Cmax of the drug. The LPS treated group showed significant bradypnea, bradycardia and low heart rate frequency as observed, through elongated peaks (RR) and (MAP) respectively and finally death after 95 minutes of LPS injection. The PTX and BT (3gm/kg) pretreatment significantly prevented these changes (dose-dependent in the BT group). The survival was maintained up to 190 min after LPS. The Pentoxifylline showed a better response (75%) than Bronco T (72%). In both the treatments, a significant decrease in pulmonary water content and minimal neutrophil infiltration and intact alveoli-capillary membrane was seen in the transverse section (T.S) of the lungs. Conclusion: Significant improvement was noted in survival time, lesser tissue damage and better lung physiology by treating with Bronco T in LPS induced septicemia.

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Necroptosis protects against exacerbation of acute pancreatitis

Cell Death and Disease ◽

10.1038/s41419-021-03847-w ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Michittra Boonchan ◽

Hideki Arimochi ◽

Kunihiro Otsuka ◽

Tomoko Kobayashi ◽

Hisanori Uehara ◽

...

Keyword(s):

Acute Pancreatitis ◽

Necrotizing Pancreatitis ◽

Neutrophil Infiltration ◽

Dependent Manner ◽

Protective Effects ◽

Interacting Protein ◽

Inflammatory Conditions ◽

Edematous Pancreatitis ◽

Genetic Deletion ◽

Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

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Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

Scientific Reports ◽

10.1038/s41598-021-92991-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benjamin N. Nelson ◽

Savannah G. Beakley ◽

Sierra Posey ◽

Brittney Conn ◽

Emma Maritz ◽

...

Keyword(s):

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Mammalian Cells ◽

Cysteine Proteases ◽

Dependent Manner ◽

Life Threatening ◽

Opportunistic Fungal Pathogen ◽

Dose Dependent ◽

Lysosomal Proteins

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.

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Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

Alternatives to Laboratory Animals ◽

10.1177/026119298801600108 ◽

1988 ◽

Vol 16 (1) ◽

pp. 32-37

Author(s):

Margherita Ferro ◽

Anna Maria Bassi ◽

Giorgio Nanni

Keyword(s):

Cell Lines ◽

Cell Cultures ◽

Membrane Lipids ◽

Hepatoma Cell ◽

Positive Control ◽

In Vitro Models ◽

Low Concentrations ◽

Formation Efficiency ◽

Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

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Cissus Quadrangularis enhances UCP1 mRNA, indicative of white adipocyte browning and decreases central obesity in humans in a randomized trial

Scientific Reports ◽

10.1038/s41598-021-81606-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Saimai Chatree ◽

Chantacha Sitticharoon ◽

Pailin Maikaew ◽

Kitchaya Pongwattanapakin ◽

Issarawan Keadkraichaiwat ◽

...

Keyword(s):

Treated Group ◽

Dependent Manner ◽

Hip Circumference ◽

White Adipocyte ◽

Ppar Γ ◽

White Adipocytes ◽

Cissus Quadrangularis ◽

Baseline Values ◽

Dose Dependent ◽

Vehicle Treated Group

AbstractObesity is associated with the growth and expansion of adipocytes which could be decreased via several mechanisms. Cissus Quadrangularis (CQ) extract has been shown to reduce obesity in humans; however, its effect on human white adipocytes (hWA) has not been elucidated. This study aimed to investigate the effects of CQ on obesity, lipolysis, and browning of hWA. CQ treatment in obese humans significantly decreased waist circumference at week 4 and week 8 when compared with the baseline values (p < 0.05 all) and significantly decreased hip circumference at week 8 when compared with the baseline and week 4 values (p < 0.05 all). Serum leptin levels of the CQ-treated group were significantly higher at week 8 compared to baseline levels (p < 0.05). In hWA, glycerol release was reduced in the CQ-treated group when compared with the vehicle-treated group. In the browning experiment, pioglitazone, the PPAR-γ agonist, increased UCP1 mRNA when compared to vehicle (p < 0.01). Interestingly, 10, 100, and 1000 ng/ml CQ extract treatment on hWA significantly enhanced UCP1 expression in a dose-dependent manner when compared to pioglitazone treatment (p < 0.001 all). In conclusion, CQ decreased waist and hip circumferences in obese humans and enhanced UCP1 mRNA in hWA suggestive of its action via browning of hWA.

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Efficacy of Souroubea-Platanus Dietary Supplement Containing Triterpenes in Beagle Dogs Using a Thunderstorm Noise-Induced Model of Fear and Anxiety

Molecules ◽

10.3390/molecules26072049 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2049

Author(s):

Aleksandar Masic ◽

Gary Landsberg ◽

Bill Milgram ◽

Zul Merali ◽

Tony Durst ◽

...

Keyword(s):

Dietary Supplement ◽

Positive Control ◽

Controlled Study ◽

Behavioral Activity ◽

Chewable Tablet ◽

Inactivity Time ◽

Anxiety Response ◽

Fear And Anxiety ◽

Dose Dependent ◽

Increased Activity

A novel botanical dietary supplement, formulated as a chewable tablet containing a defined mixture of Souroubea spp. vine and Platanus spp. Bark, was tested as a canine anxiolytic for thunderstorm noise-induced stress (noise aversion). The tablet contained five highly stable triterpenes and delivered 10 mg of the active ingredient betulinic acid (BA) for an intended 1 mg/kg dose in a 10 kg dog. BA in tablets was stable for 30 months in storage at 23 °C. Efficacy of the tablets in reducing anxiety in dogs was assessed in a blinded, placebo-controlled study by recording changes in blood cortisol levels and measures of behavioral activity in response to recorded intermittent thunder. Sixty beagles were assigned into groups receiving: placebo, 0.5×, 1×, 2×, and 4× dose, or the positive control (diazepam), for five days. Reduction in anxiety measures was partially dose-dependent and the 1× dose was effective in reducing inactivity time (p = 0.0111) or increased activity time (p = 0.0299) compared with placebo, indicating a decrease in anxiety response. Cortisol measures also showed a dose-dependent reduction in cortisol in dogs treated with the test tablet.

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Hydroxyl Safflower Yellow Pigment A (HSYA) Improves Vascular Endothelial Injury Induced by Lipopolysaccharide In Vitro Study

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2596 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1792-1798

Author(s):

Li Yan ◽

Ge Jingping ◽

Yin Yuanyuan ◽

Li Xiaomei ◽

Zhao Boxiang ◽

...

Keyword(s):

Cell Proliferation ◽

In Vitro Study ◽

Treated Group ◽

Yellow Pigment ◽

Endothelial Injury ◽

Vitro Study ◽

Vascular Endothelial ◽

Treatment Groups ◽

Dose Dependent

Aim: This research was to investigate the effects and mechanisms of HSYA in vascular endothelial injury by vitro study. Methods: Dividing HUVECs as Normal Control (NC), Model (LPS treated) group, HSYA-L, HSYA-M and HSYA-H groups. Cells in the HSYA treatment groups were treated with LPS, followed by 40 mg/ml, 80 mg/ml, and 120 mg/ml HSYA intervention (HSYA-L, HSYA-M, and HSYA -H groups), respectively. Measuring the cell proliferation, apoptosis, relative proteins and mRNA (TLR4, MyD88 and NF-κB(p65)) expressions by MTT, Flow cytometry, WB and RT-qPCR assay. Using cellular immunofluorescence to evaluate NF-κB(p65) nuclear volume of difference groups. Results: With HSYA supplement, the cell proliferation rates were significantly up-regulation with cell apoptosis significantly down-regulation with TLR4 relatived mRNA and proteins and NF-κB(p65) nuclear significantly depressed with dose-dependent (P <0.05, respectively). Conclusion: HSYA improved vascular endothelial injury induced by LPS via TLR4 pathway In Vitro.

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Amelioration of caffeine-induced seizures by modulators of sigma, N-methyl-d-Aspartate and ryanodine receptors in mice

International Journal of Epilepsy ◽

10.1016/j.ijep.2017.09.003 ◽

2017 ◽

Vol 04 (02) ◽

pp. 144-149

Author(s):

Mojtaba Keshavarz ◽

Seyyed Hoseini ◽

Samad Akbarzadeh

Keyword(s):

Receptor Antagonist ◽

Synergistic Effects ◽

Ryanodine Receptors ◽

Treated Group ◽

Nmda Receptor Antagonist ◽

Clonic Seizure ◽

Positive Control ◽

Control Group ◽

Gamma Aminobutyric Acid ◽

Clonic Seizures

AbstractObjectives The aim of this study was to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, diazepam, ketamine, an N-methyl-d-Aspartate (NMDA) receptor antagonist, and dantrolene, a ryanodine receptor antagonist, against caffeine-induced seizures in mice.Methods We used caffeine (1000 mg/kg) intraperitoneally for inducing clonic and tonic-clonic seizures in male albino Swiss strain of mice. We used opipramol in three different doses (10, 20 and 50 mg/kg), ketamine (50 mg/kg), dantrolene (40 mg/kg), opipramol (20 mg/kg) plus ketamine (50 mg/kg), opipramol (20 mg/kg) plus dantrolene (40 mg/kg), diazepam (5 mg/kg as a positive control) and the vehicle 30 min before injecting caffeine. We recorded the onset of clonic, tonic-clonic seizures and the time of death of animals after using caffeine.Results Animals treated with opipramol at a dose of 50 mg/kg or diazepam had a higher onset of clonic seizure compared with the vehicle-treated group. Dantrolene alone or with opipramol (20 mg/kg) increased the latency of clonic seizure compared with the control group. Opipramol (20 and 50 mg/kg), diazepam, ketamine alone or with opipramol, and dantrolene plus opipramol increased the latency of tonic-clonic seizures in mice. All the treatments except opipramol (10 mg/kg) and dantrolene alone increased the latency of death of animals.Conclusion Opipramol attenuated seizures produced by high doses of caffeine. Moreover, the activation of sigma receptors and inhibition of ryanodine receptors may produce synergistic effects against caffeine-induced seizures. Our study may imply that different mechanisms such as inhibition of gamma-aminobutyric acid-A receptors, activation of NMDA and ryanodine receptors may contribute to the caffeine-induced seizures.

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Evaluation of a poly-herbal preparation for the treatment of peptic ulcer

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v12i2.29980 ◽

2017 ◽

Vol 12 (2) ◽

pp. 11

Author(s):

Zaman Hayat ◽

Mueen Ahmad Chaudhry ◽

. Alamgeer

Keyword(s):

Peptic Ulcer ◽

Gastric Ulcer ◽

Treated Group ◽

Ulcer Formation ◽

Ulcer Index ◽

Herbal Formulation ◽

High K ◽

Ulcer Model ◽

Dose Dependent ◽

Gross Examination

The aim of this study was to validate the traditional uses of ulcerene, a poly-herbal formulation in ethanol, aspirin and stress-induced gastric ulcer model of rat. The extent of gastric ulcer formation was studied, using ulcer score, ulcer index, percentage cure through gross examination and histopathological evaluation. A significant (p<0.001) dose-dependent anti-ulcerant effect was observed in ulcerene (50 and 100 mg/kg)-treated group with highest effectiveness against ethanol-induced ulcer. The concentration-dependent spasmolytic effect was seen in spontaneously contracting, high K+ (80 mM) and carbachol (1 µM)-induced jejunum contractions (10, 0.3 and 1 mg/mL), similar to dicyclomine (10, 1 and 3 µM), indicated non-specific spasmolytic mechanism behind the effect. By considering these results, ulcerene can be suggested for the treatment of peptic ulcer.

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Effect of Bee Venom Pharmacopuncture on Inflammation in Mouse Model of Induced Atopic Dermatitis

Journal of Acupuncture Research ◽

10.13045/jar.2020.00122 ◽

2020 ◽

Vol 37 (2) ◽

pp. 123-127

Author(s):

Kyeong Ju Park ◽

Ho-Sueb Song

Keyword(s):

Atopic Dermatitis ◽

Mouse Model ◽

Treated Group ◽

Bee Venom ◽

Related Protein ◽

Griess Reaction ◽

Cox 2 ◽

Dose Dependent Decrease ◽

Dose Dependent ◽

Inflammatory Effect

Background: This study was designed using a mouse model of atopic dermatitis [phthalic anhydride (PA)-treated mice], to investigate the anti-inflammatory effect of bee venom pharmacopuncture (BVP) in keratinocytes.Methods: Western blot analysis was performed to investigate inflammation related protein expression of iNOS, COX-2, phospho-ERK (p-ERK), and ERK, in LPS (1 μg/mL)-activated keratinocytes, following BVP treatment, and in PA-treated mice, after BVP treatment. Griess reaction was performed to investigate NO concentration. Enzyme-linked immunosorbent assays were used to determine the concentrations of interleukin (IL)-4+, IL-17A+, IL-13 and IL-4 in PA-treated mice after BVP treatment. In addition, monocyte, macrophage, neutrophil, and eosinophil counts were measured to observe the changes in white blood cell infiltration.Results: The keratinocytes of the BVP-treated group showed a decreased expression of iNOS, COX-2, ERK at 5 OX-2, ERK E, and p-ERK at 1, 2 and 5 RKRK ERK ERK, and a dose-dependent decrease in NO concentration at 2 and 5 ntrationof s. In the BVP-treated groups (0.1 μ.1-trea μ.1-treated gr), PA-treated mice showed recovery after 4 weeks which was dose-dependent, showing a significant decrease in clinical scores for AD, and a decreased concentration of IL-13 and IL-4 with BV treatment. There was a dose-dependent decrease in the infiltration of eosinophils, neutrophils, monocytes, macrophages, and a decreased thickness of the epidermis due to inflammation, and decreased expressions of iNOS, COX-2, p-ERK, ERK, especially in the 0.1 μ0/mL BVP-treated group, Conclusion: These results suggest that BVP may be an effective alternative treatment for atopic dermatitis.

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EKSPRESI Tumor Necrosis Factor alpha (TNF-α) DAN Transforming growth factors beta (TGF-β) PADA PERIODONTITIS APIKALIS KRONIS AKIBAT INDUKSI Enterococcus faecalis PADA TIKUS WISTAR

Conservative Dentistry Journal ◽

10.20473/cdj.v7i2.2017.66-73 ◽

2019 ◽

Vol 7 (2) ◽

pp. 66

Author(s):

Richard Fritzgerald ◽

Cecilia Lunardhi ◽

Ruslan Effendy ◽

Tamara Yuanita

Keyword(s):

Tissue Damage ◽

Treated Group ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Transforming Growth Factors ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Background. Root canal treatment is a main role in decreasing infection from root canal and pulp. The main cause of periapical damage mostly are bacteries. E.faecalis is a bactery that is found as an etiology of endodontic treatment failure. Cell wall of this bacteria is containing Lipoteichoic acid (LTA). LTA can penetrate into the periradicular tissue, act as endotoxin in host and cause periradicular inflammation then lead to bone destruction. LTA stimulates immunology reaction that produce Tumor Necrosis Factor alpha (TNF-α) and Transforming growth factors beta (TGF-ß). TNF-α is a main mediator and also have an important role in inflamation response otherwise TGF-ß is working as a multifunction regulator of cell growth and differentiation during reforming and remodelling. Purpose. The aim of this study is to know about the expression of TNF-α and TGF-ß during the periapical tissue damage due to induction of E.faecalis. Method. This study used laboratory experimental with the post test only control group design. A total of 30 male rats were randomly divided into 3 main groups, Group A (control negative) : normal tooth. Group B (control positive) : every tooth was induced only by sterile BHI-b. Group C (treated group) : every tooth was induced by 10 μl BHI-b E.faecalis ATCC212(106 CFU). The animals were sacrificed 21 days later and prepared for histological examination of tissue damage, then we did the immunohistochemistry followed by calculation on the light microscope. Result. The analysis revealed that the expression of TNF-α at treated group are higher than negative control and positive control but the expression of TGF-ß at treated group are higher than the negative control group but lower than positive control. Conclusion. From this study we know that the expression of TNF-α and TGF-ß are changing during the periapical tissue damage that induced by E.faecalis.

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