Anti-inflammatory and wound healing properties of Malaysia tualang honey

Inflammation is a biological response and a defence mechanism by the body to remove harmful stimuli followed by the healing process. Healing is a process of skin and other soft tissue repair at the site of injury. However, uncontrolled inflammation could lead to serious illnesses such as cancer and cardiovascular diseases, which cause great impact on public health and economy. This necessitates supplementation with anti-inflammatory properties to prevent or remove unnecessary inflammation and damage. For ages, Tualang honey (TH) has been used as a natural remedy for inflammation and wounds. TH also exhibits antioxidant, antibacterial and reproductive properties. This review collates the various studies on anti-inflammatory and wound-healing properties of TH. It also presents findings that indicate that honey may ameliorate ultraviolet-induced inflammation of the skin, chemical-induced inflammation of the eyes and oxidative stress on the eyes. Besides, wound-healing properties have also been highlighted here. These data suggest that TH might be a therapeutic agent in the management of inflammation and wound healing. However, there is a need to study the underlying mechanism of action of TH in vitro and in vivo, to develop a better understanding of its potential benefits

Discovery of endothelial barrier protection by natural product

Vascular endothelial cells emerge as a key regulator of vascular homeostasis. Disruption of vascular endothelial barrier leads to vascular hyperpermeability which in turn contributes to a broad spectrum of the most dreadful of human diseases, including heart diseases, diabetes, atherosclerosis, and cancer. The search for permeability-modulating agent still far lacking, thus, it is a need to search for a new agent to reduce endothelial hyperpermeability. Bixa orellana L. has been traditionally used to treat a number of ailments, including internal inflammation. Preliminary data showed that its leaves are able to suppress inflammation induced by carrageenan. Hence, this study aimed to investigate the anti-hyperpermebility effect of B. orellana leaf extract (AEBO) and elucidate its mechanism of action induced by histamine. The anti-hyperpermeability activity of the extract was evaluated using histamineinduced rat paw oedema, increased peritoneal vascular permeability, nitric oxide (NO) and vascular endothelial growth factor (VEGF) measurement in animal model, while, phospholipase C (PLC) – NO – cyclic guanosine monophosphate (cGMP) signaling pathway was determined via in vitro. AEBO produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with maximal percentage of inhibition (60.25%) achieved with a dose of 150 mg/kg. Up to 90% of increased peritoneal vascular hyperpermeability successfully suppressed by AEBO. NO and VEGF from inflammed paw tissues was also found to be downregulated in the AEBO group. Histamine-induced increased endothelial permeability was significantly attenuated by pretreatment with AEBO in a time- and concentration-dependent manner. Moreover, AEBO also suppressed PLC, calcium, NO and cGMP signaling cascade when endothelial cells were challenged with histamine. Protein kinase C activity was also significantly abolished by AEBO under histamine condition. In conclusion, the present data suggest that AEBO could suppress histamine-induced increased vascular permeability and the activity may be closely related with the inhibition of the PLCNO-cGMP signaling and PKC activity

Regression of solid breast tumours in mice by Newcastle disease virus is associated with production of apoptosis related-cytokines

Different strains of Newcastle disease virus (NDV) worldwide proved to have tumouricidal activity in several types of cancer cells. However, the possible anti-cancer activity of Malaysian NDV AF2240 strain and its mechanism of action remains unknown. The ability of cytokine-related apoptosis-inducing NDV AF2240 to treat breast cancer was investigated in the current study. Methods A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes). Results The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines. Conclusions NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus. Electronic supplementary material The online version of this article (10.1186/s12885-019-5516-5) contains supplementary material, which is available to authorized users

Bixa orellana leaves extract inhibits bradykinin-induced inflammation through suppression of nitric oxide production

Objective: The present study was conducted to assess the anti-inflammatory effect of a crude aqueous extract of Bixa orellana leaves (AEBO) and to examine the possible involvement of nitric oxide (NO) in its anti-inflammatory mechanism. Materials and Methods: The air-dried, powdered leaves were soaked in distilled water (1:20 w/v) at 50°C for 24 h and the supernatant obtained was freeze-dried (yield 8.5% w/w). The dosage was recorded as the mass of extract per kg b.w. of rats in all inflammatory assays (bradykinin-induced paw edema, peritoneal vascular permeability and NO assay). Results: Pretreatment with AEBO for 4 consecutive days exhibited significant inhibitory activity against inflammatory models, the bradykinin-induced hind paw edema model and bradykinin-induced increased peritoneal vascular permeability at both doses in dose-dependent manner. In addition, AEBO was also found to significantly suppress the production of NO at doses of 50 and 150 mg/kg. Conclusion: This study provides scientific data to support the traditional use of B. orellana leaves in treating inflammation. Results from this study suggest that AEBO exerts anti-inflammatory effects. Part of this anti-inflammatory effect may be associated with its antibradykinin activity and may be related to a reduction of the NO production

Human wharton’s jelly-derived mesenchymal stem cells minimally improve the growth kinetics and cardiomyocyte differentiation of aged murine cardiac c-kit cells in in vitro without rejuvenating effect

Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton’s Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell–cell contact, the effect is minimal

Suppression of histamine-induced increase of endothelial permeability via nitric oxide production by Bixa orellana leaves extract

Previously reported pharmacological activity of Bixa orellana L. (Bixaceae) includes its ability to neutralize edema-forming effects of Bothrops asper venom (Nunez V., et al, 2004). Study on the mechanism of its anti-edema activity is thus far lacking. The purpose of this study was to examine the effects of aqueous extract of B. orellana (AEBO) leaves on endothelial permeability and the permeability-regulator molecule, nitric oxide (NO), during inflammatory stimulation by histamine. This study demonstrated that AEBO (0.1mg/ml -0.4mg/ml) significantly (p<0.05) suppressed histamine-induced increased endothelial permeability in human umbilical veins endothelial cells (HUVECs), where maximal inhibition was 90.2% at concentration and time point of 0.4mg/ml and 15min, respectively. Histamine-mediated NO formation in HUVECs was significantly reduced by all concentration of AEBO in a dose-dependent manner. 0.4mg/ml showed maximal inhibition where it reduced NO level from 12.51±0.07µM to 11.3±0.07µM (65.4% inhibition). On the other hand, 0.1 and 0.2mg/ml of AEBO suppressed NO production at 21.70% and 34.50%, respectively. To verify that AEBO will produce similar effects to exogenous source of NO as to endogenous NO, NO donor, sodium nitroprusside (SNP) was used. AEBO showed significant effects in scavenging NO radicals released by SNP where maximal inhibition was 51.2% at 0.4mg/ml. These results indicate that AEBO suppressed increased endothelial permeability by re-establishing normal NO production in HUVECs. This study justifies the use of Bixa orellana in traditional medicine by showing its potential in regulating endothelial cell barrier function

Malaysian Tualang honey inhibits hydrogen peroxide-induced endothelial hyperpermeability

Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H2O2-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H2O2 was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (p < 0 05), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (p < 0 05) reduced H2O2 (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and β-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (p < 0 05) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H2O2. These results suggested that TH could inhibit H2O2-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability

Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines

Clinacanthus nutans Lindau leaves (CN) have been used in traditionalmedicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T, K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals, but less effective in negating nitric oxide and hydrogen peroxide radicals. Chloroformextract exerted the highest antiproliferative effect on K-562 (91.28±0.03%) andRaji cell lines (88.97± 1.07%) at 10

Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract

The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg⁻¹) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150 mg kg⁻¹. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release