Effects of Korean red ginseng extract on the prevention of atopic dermatitis and its mechanism on early lesions in a murine model

Ethnopharmacological relevance

Korean red ginseng (KRG) has been shown to possess various biological activities including anti-inflammatory properties.

Aim of the study

We aimed to investigate the effects and mechanism of KRG on the prevention of atopic dermatitis (AD) using a mouse model.

Materials and methods

The effect of KRG in trinitrochlorobenzene (TNCB)-treated NC/Nga mice was assessed by measuring ear thickness, transepidermal water loss (TEWL), total serum IgE, histologic changes of lesional skin, mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor (TNF)-α, immunohistochemistry for tissue interleukin (IL)-4, IL-17, and interferon (IFN)-γ.

Results

KRG significantly reduced ear thickness. Oral administration of KRG significantly prevented the increase in TEWL induced by TNCB. The serum IgE level was significantly lower in the KRG group. Histologically, lymphocyte infiltration was markedly decreased by KRG. CD1a positive (CD1a+) cells were diminished by KRG. Immunohistochemically, KRG significantly suppressed the protein expression of TSLP and TNF-α. The mRNA expression of TSLP in the lesions was significantly reduced by KRG. These results demonstrate that oral administration of KRG may inhibit the development of AD-like skin lesions in NC/Nga mice by modifying TSLP, DCs, and at least in part, the Th2 response.

Conclusion

KRG may be a potential therapeutic modality for the prevention of AD.     

Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin lesions in NC/Nga mice

Aim of the study

Chelidonium majus (CM) has traditionally been used for treatment of various inflammatory diseases including atopic dermatitis (AD). However its action on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of CM on AD using NC/Nga mice as an AD model.

Materials and methods

The effect of CM on 1-chloro-2,4-dinitrobenzene (DNCB) induced NC/Nga mice was evaluated by examining skin symptom severity, itching behavior, ear thickness, levels of serum immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), and interlukin-4 (IL-4), skin histology.

Results

The CM significantly reduced the total clinical severity score, itching behavior, ear thickness and the level of serum IgE in AD mouse model. CM not only decreased TNF-α but also IL-4.

Conclusion

These results suggest that CM may be a potential therapeutic modality for AD.     

Suppression of dust mite extract and 2,4-dinitrochlorobenzene-induced atopic dermatitis by the water extract of Lindera obtusiloba

Ethnopharmacological relevance

The Lindera obtusiloba has been used in traditional medicine for the treatment of inflammation and dermatitis. In this study, we investigated the effect of topical application of Lindera obtusiloba water extract (LOWE) on the house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD).

Materials and methods

We established AD model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. After a topical application of LOWE on the skin lesions, the epidermal thickness, mast cell infiltration, and serum immunoglobulin E (IgE) and histamine were measured. In addition, the gene expression of interleukin (IL)-4, IL-13, IL-31, and tumor necrosis factor (TNF)-α in the ears was assayed.

Results

LOWE reduced AD symptoms based on ear thickness, histopathological analysis, and serum IgE levels. LOWE inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. Moreover, LOWE suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears.

Conclusions

Our results showed that topical application of LOWE exerts beneficial effects in AD symptoms, suggesting that LOWE might be a candidate for the treatment of AD.     

Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice

Aim of the study

The bark of Alnus species has long been used in traditional oriental medicine in the treatment of many pathological conditions, including fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic herpes, eczema and prurigo), and inflammation. In order to assess the immunomodulatory efficacy of a novel herbal medicine in treating atopic dermatitis, we measured serum levels of several allergic and inflammatory biomarkers in NC/Nga mice before and after treatment with this experimental agent.

Materials and methods

Gene and protein expression analyses of iNOS and COX-2 were quantified by real time PCR and Western blot analysis and serum levels of IL-4, -5 and -13 were also measured by ELISA, all of which were reduced after treatment with the experimental agent. Additionally, serum concentrations of IgE and blood eosinophil counts were reduced in treated mice.

Results

The topical application of leaf and bark extract from Alnus japonica suppressed the development of AD-like skin lesions. The percent of blood eosinophils was decreased after treatment with leaf and bark extract from Alnus japonica. The serum IgE and Th2-related cytokine levels were decreased after treatment with leaf and bark extract from Alnus japonica compared with those treated with base cream (vehicle treated AD group). The IL-4, IL-5 and IL-13 were lower than those of vehicle treated AD group.

Conclusions

We contend that leaf and bark extract from Alnus japonica may prove useful in the treatment of atopic dermatitis and other allergic skin diseases, although more in-depth clinical studies are necessary before clinical implementation.     

Korean red ginseng (Panax ginseng) ameliorates type 1 diabetes and restores immune cell compartments

Ethnopharmacological relevance

Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential.

Aim

This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D).

Materials and methods

The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed.

Results

KRG extract significantly lowered blood glucose levels to an average of 250 mg/dl from 350 mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis.

Conclusion

This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects.     

Topical application of Rehmannia glutinosa extract inhibits mite allergen-induced atopic dermatitis in NC/Nga mice

Aim of the study

Rehmannia glutinosa is known in Asia as a traditional herbal medicine with anti-inflammatory properties. Atopic dermatitis (AD) is an inflammatory skin disease associated with enhanced T-helper 2 (Th2) lymphocyte responses to allergens that results in elevated serum IgE levels and leukocyte infiltration. Although some studies have shown that Rehmannia glutinosa extract (RGE) has anti-inflammatory and anti-allergic activities, these properties have not been demonstrated in AD. This study investigated the effectiveness of RGE as a therapeutic candidate in an AD model as well as its underlying mechanism of action.

Materials and methods

The effects of RGE on mite allergen (Dermatophagoides farinae)-treated NC/Nga mice were evaluated by skin symptom severity, ear thickness, production of serum IgE and histamine, and expression of cytokines, chemokines, and adhesion molecules in the ear lesions. In addition, the levels of thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), and regulated on activation, normal T cell expressed and secreted (RANTES) produced in both TNF-α- and IFN-γ-stimulated human keratinocytes were investigated by enzyme-linked immunosorbent assay (ELISA).

Results

RGE treatment of NC/Nga mice significantly reduced dermatitis scores, ear thicknesses, and serum histamine levels. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. In the ear lesions, mRNA expression levels of IL-4, TNF-α, VCAM-1, and ICAM-1 were inhibited by RGE treatment. RGE also suppressed the production of TARC, MDC, and RANTES in both the ear lesions and keratinocytes.

Conclusions

RGE inhibits the development of AD in NC/Nga mice by suppressing the expression of cytokines, chemokines, and adhesion molecules.     

Anti-inflammatory effects of ethanolic extract from Lagerstroemia indica on airway inflammation in mice

Aim of the study

In the present study, we investigated whether the Lagerstroemia indica Linn (LI) extract has an anti-inflammatory effect on lung inflammation in ovalbumin-induced asthmatic mice.

Materials and methods

The LI extract was obtained from dried and powdered whole plants of LI using 80% ethanol. ELISA was performed to evaluate cytokine concentration. BALB/c mice were used as a mouse model of asthma after asthmatic induction by ovalbumin sensitization and inhalation. We examined the effects of the LI extract on leukocyte infiltration and mucus secretion using cell count and histological stain.

Results

The amount of cytokines, such as interleukin (IL)-2, IL-4, IL-5, IL-13, and TNF-α, was increased in Jurkat cells using the extract from house dust mites. Increased cytokine concentrations were inhibited by the LI extract. The LI extract suppressed the increased expression of IL-6 after treatment with mite extract of EoL-1 cells and THP-1 cells. In an in vivo experiment using asthmatic mice, the LI extract significantly inhibited leukocytosis and eosinophilia in bronchoalveolar lavage (BAL) fluid and lung tissue samples. The LI extract inhibited the increase in mucus secretion by goblet cells, blocked the production of reactive oxygen species in BAL fluid cells, and blocked the protein expression of IL-5 in BAL fluid. The concentration of ovalbumin-specific IgE in BAL fluid was weakly inhibited by the LI extract.

Conclusions

These results suggest that the LI extract may be used as a valuable agent for treating allergic diseases such as asthma due to its anti-inflammatory property.     

Selective Th1 upregulation by ethyl acetate fraction of Labisia pumila

Aim of the study

Labisia pumila has rejuvenating properties that help women to regain the strength and vigour after giving birth (Burkill, 1935) leading us to speculate that Labisia pumila might also modulate the immune matrix as it is one of the important aspect of healthy state of the living body.

Materials and methods

Studies were carried out for the evaluation of pro-inflammatory cytokines in murine neutrophils followed by expression of T cell-surface markers and corresponding intracellular expression of cytokines related to T helper1 (Th1) and T helper 2 (Th2) activity.

Results

The ethyl acetate fraction (A001/3b) obtained from ethanolic extract of leaves of Labisia pumila at graded doses (in vitro) showed increased expression of TNF-α, IL-6 and IL-12. IL-12 is a strong inducer of Th1 response in activated CD4+ T cells and accordingly T cell studies were carried out (in vivo). These specific studies showed A001/3b to cause marked stimulation of CD4+ T helper cells and related cytokine expression like IL-2 and IFN-gamma (a potent Th1 inducer), thereby, having a predominant Th1 upregulation pathway. This was further validated by suppression of IL-4 and IL-10 expression which are the Th2 pathway cytokines.

Conclusion

This study showed ethyl acetate fraction (A001/3b) of Labisia pumila to have Th1 upregulating activity and suggests its possible usefulness as a therapeutic agent in immune compromised patients.     

Inhibition of 2,4-dinitrofluorobenzene-induced atopic dermatitis by topical application of the butanol extract of Cordyceps bassiana in NC/Nga mice

Ethnopharmacological significance

The Cordyceps species are insect-borne mushrooms that have been ethnopharmacologically used for skin diseases such as eczema and dermatitis.

Aim of the study

In this study, we investigated the curative effects of the butanol fraction (CBBF) of Cordyceps bassiana on atopic dermatitis.

Materials and methods

Dermatitis was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. After a topical application of CBBF on the skin lesions, the dermatitis score, epidermal thickness, mast cell number, and interleukin (IL)-4 and interferon (IFN)-γ, as well as the levels of histamine and immunoglobulin E (IgE) in the serum, were measured. Moreover, effect of CBBF on histamine release was examined using RBL-2H3 under stimulation with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA).

Results

CBBF inhibited atopic dermatitis symptoms and signs in the DNFB-treated NC/Nga mice. The suppressive activity of topically applied CBBF may be due to the dose-dependent blockade of a series of immunopathological events, including the release of histamine, the production of IgE, and the secretion of IL-4 and IFN-γ. However, this extract did not directly suppress the degranulation process, assessed by measuring β-hexosaminidase release.

Conclusions

Our results suggest that CBBF can be applied as an effective herbal remedy to treat atopic dermatitis.     

Inhibitory effects of Cinnamomum cassia extract on atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice

Aim of the study

: Cinnamomum cassia (C. cassia) has been traditionally used to treat allergic disease as well as dyspepsia, gastritis, and blood circulation disturbances. However, the antiallergic properties of C. cassia have not been fully verified using scientific tools. This study investigated the effectiveness of C. cassia extract (CCE) as an antiallergic agent in atopic dermatitis model and underlying mechanism.

Materials and methods

: The effect of CCE on mite antigen-treated NC/Nga mice was evaluated by examining skin symptom severity, levels of serum IgE, tumor necrosis factor-α (TNF-α), and histamine, skin histology, and mRNA expression of cytokines in the skin lesions. Moreover, the effect of CCE on TNF-α-and interferon-γ (IFN-γ)-induced chemokine production in human keratinocytes was investigated using ELISA.

Results

: CCE treatment of NC/Nga mice reduced the dermatitis score and the levels of serum IgE, histamine, and TNF-α. Histological examination showed inhibition of the thickening of the epidermis/dermis and reduced dermal infiltration of inflammatory cells. In skin lesions, mRNA expression of IL-4, TNF-α, and thymus and activation-regulated chemokine (TARC) was inhibited by CCE treatment. The production of TARC, macrophage-derived chemokine, and RANTES from IFN-γ-and TNF-α-stimulated human keratinocytes was suppressed by CCE treatment in a dose-dependent manner.

Conclusions

: CCE inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response.     

Topical application of porcine placenta extract inhibits the progression of experimental contact hypersensitivity

Aim of study

Placenta extract features as a composition of ointments used for skin beautification, dermatological diseases and skin dryness. However, little evidence has been cited about its underlying mechanisms of action by which it exerts a beneficial role in dermatological diseases in vivo. In this study, we intended to test the effect of topical application of porcine placenta extract in mouse model of contact hypersensitivity and elucidate its mechanism of action.

Materials and methods

To test the in vitro effect of porcine placenta extract, RAW 264.7 cells were cocultured with porcine placenta extract and stimulated with LPS (1 μg/ml) and the expression of inflammatory mediator TNF-α was estimated by RT-PCR at the mRNA level and by intracellular staining at the protein level. To further test in vivo efficacy, porcine placenta extract was topically applied to the mice with experimental skin hypersensitivity. For in vivo studies placenta extract in gel form was topically applied to ear of DNCB-induced contact hypersensitivity mouse model everyday for 2 weeks and progression of the disease was estimated by following criteria: (a) ear thickness, (b) serum IgE level by ELISA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total cells and CD4⁺ T cells by real time PCR.

Results

Topical application of porcine placenta extract on mouse ears with contact hypersensitivity decreased the severity and progression of the disease manifested by reducing ear swelling, inflammation and edema. Histological evaluation showed that placenta extract treatment reduced lymphocyte infiltration in the ear tissues. Protective effect of placenta extract is also associated with down-regulation of serum IgE level and inflammatory cytokine production (IL-1β, IFN-γ, TNF-α, IL-4, IL-12 and IL-17) in total lymph node cells and CD4⁺ T cells.

Conclusions

Our data indicate that protective effect of porcine placenta extract in contact hypersensitivity is mediated by inhibition of the inflammatory responses and IgE production, suggesting a potential therapeutic application of porcine placenta extract to modulate skin inflammation.     

The memory-enhancing effects of Kami-ondam-tang in mice

Ethnopharmacological relevance

Kami-ondam-tang (KOT), a traditional Chinese medicine, has been used to treat mental and neuropsychiatric disorders, including dementia. This study aimed to investigate the effects of KOT on cognition and the mechanisms underlying these effects in mice.

Materials and methods

Using the passive avoidance task, we investigated the effect of sub-chronic administration of KOT on the cognition of mice. We also examined the expressions of protein kinase B (Akt), cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and doublecortin (DCX) in the hippocampal CA1 and dentate gyrus regions using immunohistochemistry and western blotting.

Results

The administration of KOT (50 mg/kg/day, p.o.) for 14 days significantly increased step-through latency in the passive avoidance task compared with vehicle-treated controls. Furthermore, KOT administration (50 mg/kg/day, p.o.) significantly increased the expressions of phosphorylated Akt, phosphorylated CREB and BDNF in the hippocampal CA1 and dentate gyrus. In addition, KOT administration resulted in a significant increase in the number of DCX-immunopositive cells in the dentate gyrus.

Conclusions

These results suggest that KOT enhances cognitive performance through the upregulation of Akt-CREB-BDNF signaling and neurogenesis.     

The hypoglycemic activity of Lithocarpus polystachyus Rehd. leaves in the experimental hyperglycemic rats

Ethnopharmacological relevance

Leaves of Lithocarpus polystachyus Rehd. are used for the treatment of disorders such as diabetes, hypertension, and epilepsy in folk medicine of South China. The possible antidiabetic effects of the leaves were investigated in experimental type 2 and type 1 diabetic rats.

Materials and methods

Type 2 diabetic rats received orally three different extracts of Lithocarpus polystachyus Rehd. leaves for 4 weeks (aqueous extract [ST-1], ethanol extract [ST-2], flavonoid-rich fraction [ST-3]). At the end of the experiment biochemical parameters were tested and livers and pancreases were excised for histological study. After the comparison of the pharmacological test results of the three extracts, the one which showed the best bioactivity was further studied to confirm its antidiabetes effect on both type 2 and type 1 diabetic rats.

Results

Compared to ST-1 and ST-2, ST-3 had better effects on regulation of blood glucose, glycosylated serum protein, cholesterol, triglyceride, malondialdehyde, superoxide dismutase and attenuation of liver injury in type 2 diabetic rats (p < 0.01 or p < 0.05). ST-3 administration for four weeks also significantly reduced the fasting serum insulin and C-peptide level and improved the insulin tolerance (p < 0.05). In type 1 diabetic rats, ST-3 supplement for three weeks caused significant reduction in fasting blood glucose, total cholesterol, triglyceride, urea nitrogen, creatinine and liver mass, along with significantly inhibiting the decline of insulin level compared to diabetic control (p < 0.05 or p < 0.01).

Conclusion

The flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves (ST-3) had better beneficial effect than that of the ethanol or aqueous extract in experimental diabetic rats, which means that the bioactivity of the herbal leaves is probably due to the presence of flavonoids. The results also strongly suggest that the antidiabetic effect of ST-3 was possibly through multiple mechanisms of action including blood lipid and antioxidant mediation. The results indicated that the aqueous flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves possessed significant protective activity in type 2 and type 1 diabetes.     

Therapeutic effects of total coumarins from Urtica dentata Hand on collagen-induced arthritis in Balb/c mice

Ethnopharmacological relevance

Urtica dentata Hand (UDH), the root of Laportea bulbifera (Sieb. et. Zucc.) Wedd, has long been utilized in traditional Chinese medicine for the treatment of rheumatoid arthritis and some other autoimmune diseases. Coumarins are the main active principles contributing to UDH's efficacy, but the mechanisms have not been fully clarified.

Aim of study

To explore effects of total coumarins (TC) isolated from UDH on the development of type II collagen (CII)-induced arthritis (CIA) in Balb/c mice.

Materials and methods

Arthritis was induced in Balb/c mice by immunization with an emulsion of 200 mg CII and complete Freund's adjuvant (CFA). The CIA mice were then given with a suspension of TC or saline by intragastric (i.g.) administration every other day. The incidence and severity of disease and histopathology of inflammation were assessed. Inflammatory response was determined by measuring the levels of different inflammation mediators in serum. The effect of TC on differentiation of CD4⁺CD25⁺ Foxp3⁺Treg cells was examined by flow cytometry. The phenotype of bone marrow-derived dendritic cells (DCs), T-bet mRNA level and IL-12p70 secretion by DCs were also detected.

Results

Pharmacologically, treatment with TC for type II collagen induced arthritis in mice through oral administration displayed significant and dose-dependent drop of clinical arthritis score and paw swelling, compared with the untreated CIA mice. Pathologic changes showed that TC protected tissues against bone destruction, whereas an almost complete destruction occurred in the CIA model group. The protective status was associated with a substantial decrease in the production of IFN-γ and IL-2, an increase of IL-10 and TGF-β and suppressive expression of T-bet in DCs. TC also induced the generation of CD4⁺CD25⁺ Treg cells with a Treg phenotype Foxp3. TC-treated DCs were characterized as low expression of MHC class II and CD86 molecules, as well as a reduction of IL-12p70.

Conclusions

Our data suggest that TC provides substantial therapeutic protection against CIA by eliciting immune tolerance and it would be a valuable candidate for further investigation as a new anti-arthritic agent.     

Oral hypoglycaemic, antihyperglycaemic and antidiabetic activities of Sri Lankan Broken Orange Pekoe Fannings (BOPF) grade black tea (Camellia sinensis L.) in rats

Ethnopharmcological relevance

Sri Lankan traditional practitioners recommend the consumption of black tea infusion (BTI) made from Camellia sinensis L. plant for regulation of glycaemia. However, they do not specify the grade of tea and their origin (i.e., agroclimatic elevation) and as such many prediabetics and milddiabetics use BOPF grade tea.

Aim of the study

This study examines the blood glucose lowering potential of Sri Lankan BOPF grade tea and its potency with respect to agroclimatic elevations.

Materials and methods

Unblended orthodox BOPF grade tea samples were collected from high-, mid- and low-grown agroclimatic elevations in Sri Lanka. Different concentrations of warm BTI (60, 120 and 480 mg/ml), tolbutamide (reference drug: 22.5 mg/kg body weight) and water (control) were orally administered to different groups of rats, and hypoglycaemic and antihyperglycaemic activities were assessed. Antidiabetic activity was determined using streptozotocin induced diabetic rats. Mechanisms of blood glucose lowering actions were investigated using several standards techniques.

Results

BTI exhibited significant (P < 0.05), dose-dependent and marked hypoglycaemic and antihyperglycaemic activities with quick onset. These effects did not differ with respect to agroclimatic elevation, although there were differences in the content of phyto-constituents. BTI also showed marked and quick antidiabetic activity. BTI inhibited intestinal glucose absorption and impaired α-glucosidase and α-amylase activities. BTI possessed insulinomimetic action, ability to improve insulin sensitivity and in vivo antioxidant activity. Notably, BTI was nontoxic.

Conclusions

BTI of Sri Lankan BOPF grade tea has oral hypoglycaemic, antihyperglycaemic and antidiabetic actions which are mediated via multiple mechanisms. This study also indicates that, BOPF grade tea of any agroclimatic elevations in Sri Lanka could be used in the regulation of glycaemia.     

Induction of apoptotic cell death by Pharbitis nil extract in HER2-overexpressing MCF-7 cells

Aim of the study

We performed this study to investigate the anti-cancer activity of Pharbitis nil (PN) ethanol extract which has been used for herbal medicinal treatment against diseases in East Asia.

Materials and methods

We analyzed the effects of PN extract on proliferation of breast cancer cell lines, MCF-7 control vector (vec) and MCF-7 human epidermal growth factor receptor 2 (HER2) cells engineered to overexpress oncogenic HER2 via retroviral infection. We performed the proliferation assay to measure the growth rate of the cells. FACS analysis was used to analyze the cell cycle. Western blot analysis was used to investigate the effect of PN on the level and activation of intracellular molecules.

Results

We found that PN extract inhibited the proliferation of both MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with the increase of sub G0/G1 apoptotic fractions. When we check the efficiency of PN on the level of intracellular signaling molecules, we found that PN extract induced the inhibition of phosphorylation of HER2 and its downstream effectors, Akt and extracellular signal-regulated kinases (ERK). Active forms of both Akt and ERK were gradually decreased in PN-treated MCF-7 vec and MCF-7 HER2 cells suggesting that the growth suppressive activity of PN is related to signaling pathway. The level of cyclin D also diminished in PN-treated both cells suggesting that PN may inhibit the growth of MCF-7 vec and MCF-7 HER2 cells by perturbing cell cycle progression. It should be noted that PN decreased the growth rate of both MCF-7 vec and MCF-7 HER2 cells without changing the level and activation of p53.

Conclusion

PN extract suppressed the proliferation rate of HER-2 overexpressing MCF-7 breast cancer cells inducing apoptotic cell death in vitro. Our data demonstrates that PN extracts contain useful anti-tumor activity especially against HER2 overexpressing breast cancer.     

Wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus: a comparative study

Ethnopharmacological relevance

In Turkish folk medicine Ranunculus species are used for wound healing and for the treatment of rheumatism. The present study was conducted to evaluate in vivo wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus.

Material and methods

In vivo wound healing activity of the extracts prepared from Ranunculus pedatus and Ranunculus constantinapolitanus was evaluated by linear incision and circular excision wound models. Hydroxyproline content of the treated tissues was also assessed. We also studied the anti-inflammatory activity using Whittle method with some modifications.

Results

Methanolic extract of Ranunculus pedatus showed significant wound healing effect both in incision (31.4%) and excision (55.74%) wound models. Methanolic extract of both Ranunculus pedatus and Ranunculus constantinapolitanus demonstrated anti-inflammatory activity with the inhibition value of 26.2% and 23.3% respectively, at the dose of 100 mg/kg. Hydroxyproline content of the tissues treated with the methanolic and aqueous extracts of Ranunculus pedatus and methanolic extract of Ranunculus constantinapolitanus were found to be significantly higher than that of the other extracts.

Conclusion

The experimental data revealed that Ranunculus pedatus showed significant wound healing and anti-inflammatory effect.     

Inhibition of intestinal glucose absorption by anti-diabetic medicinal plants derived from the James Bay Cree traditional pharmacopeia

Background

Type II diabetes and obesity are major health problems worldwide and aboriginal peoples are particularly at risk. To address this problem in Canadian native populations who find modern pharmaceuticals culturally inappropriate, our team is testing the traditional pharmacopeia of the James Bay Cree for anti-diabetic and anti-obesity activities. More specifically, the aim of the present study was to define the effects of traditional plants on intestinal glucose absorption, an under-appreciated anti-hyperglycaemic and anti-obesity activity.

Methods

Crude ethanol extracts of 17 Boreal forest medicinal plants were tested in vitro using the Caco-2 human enterocytic cell line and in vivo using an oral glucose tolerance test.

Results

Thirteen of seventeen extracts were observed to significantly inhibit uptake when administered simultaneously with ³H-deoxyglucose. Inhibition was dose-dependent and, in a few cases, even surpassed that induced by a combination of the positive controls. To validate these effects in vivo, four plant extracts were administered by intragastric gavage at 250 mg/kg to normal rats simultaneously with a 3 g/kg bolus of glucose. This resulted in a decrease in peak glycaemia by approximately 40% for two of them. Similarly, only 2 extracts reduced glucose transport after long term incubation and this could be related to reductions in the expression of SGLT-1 or GLUT-2 proteins.

Conclusions

These findings indicate that competitive inhibition of intestinal glucose uptake can be achieved by crude extracts of medicinal plants. Such extracts could be taken with meals to control postprandial glycaemia and reduce caloric intake in high risk populations that are positively inclined towards traditional medicine.