Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo

Ethnopharmacological relevance

The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE).

Aim of the study

To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.

Materials and methods

Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice.

Results

AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC₅₀ of 0.41 μg/ml, and 100 mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice.

Conclusions

Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.     

Anti-atherosclerotic effects of Polygonum aviculare L. ethanol extract in ApoE knock-out mice fed a Western diet mediated via the MAPK pathway

Ethnopharmacological relevance

Polygonum aviculare L. has been used in traditional Korean medicine to treat obesity and symptoms associated with hypertension. The effectiveness or mechanism of Polygonum aviculare L. ethanol extract (PAE) on atherosclerosis disease has not been examined experimentally. This study investigated the protective effect of PAE in atherosclerotic mice.

Materials and methods

ApoE KO mice were fed a Western diet (WD) alone or with PAE or a statin for 12 weeks, followed by analysis of bodyweight, serum lipid levels, and blood pressure. Staining of the aorta and adipose tissue, expression levels of adhesion molecules, and the MAPK pathway were also examined. Cell viability, NF-κB activity, and protein levels of adhesion molecules were assessed in vitro.

Results

ApoE KO mice fed PAE (50 and 100 mg/kg) or statin (10 mg/kg) gained less body weight, and has less adipose tissue and lower serum lipid levels and blood pressures than the WD group. Aorta ICAM-1, VCAM-1, and NF-κB levels were decreased by PAE in a dose-dependent manner, consistent with the in vitro observations. PAE and statin decreased atherosclerotic plaque and adipocyte size versus the WD group. Furthermore, PAE decreased phosphorylation of MAPK pathway components in the aorta of PAE-treated mice, suggesting that PAE's anti-atherosclerotic effects are mediated via a MAPK pathway-dependent mechanism.

Conclusions

PAE may protect against the development of atherosclerotic disease. The beneficial effects are associated with lowering bodyweight, serum lipids, blood pressure, adhesion molecular protein levels, atherosclerotic plaque, and adipocyte size, involving the MAPK pathway.     

In vivo and in vitro anti-inflammatory activity of Lentinus polychrous extract

Ethnopharmacological relevance

Lentinus polychrous is a Thai local edible mushroom, traditionally used for the treatments of fever and inflammation due to snake or scorpion envenomation.

Aim of study

The present study aimed to investigate an anti-inflammatory effect of Lentinus polychrous mycelial extract (LPME) both in vitro and in vivo.

Materials and methods

The cytotoxicity and suppressive effects of LPME on nitric oxide production, intracellular O₂⁻ production, pro-inflammatory mediator expression, TNF-α production were determined by using LPS-activated RAW 264.7 cells. In addition, Anti-inflammatory effect of LPME was evaluated by using carageenan-induced paw edema in rats.

Results

The LPME exhibited cytotoxicity with 50% inhibitory concentration (IC₅₀) of 280.25±10.10 μg/ml and significantly suppressed the productions of NO and intracellular O₂⁻ with dose-dependent manner. LPME decreased the expressions of iNOS, IL-1β, IL-6, TNF-α and COX-2 and significantly decreased the TNF-α production in LPS-activated macrophage with dose-dependent manners. Moreover, LPME showed significant suppressive effect on paw edema in rats.

Conclusion

The results clearly revealed that the LPME inhibited NO and pro-inflammatory productions by down-regulating the gene expressions of pro-inflammatory mediators leading to the decrease paw edema in rat which support the traditional use.     

Screening of the topical anti-inflammatory activity of the bark of Acacia cornigera Willdenow, Byrsonima crassifolia Kunth, Sweetia panamensis Yakovlev and the leaves of Sphagneticola trilobata Hitchcock

Ethnopharmacological relevance

An investigation of topical anti-inflammatory activity was undertaken on plants used in Central America traditional medicine.

Aim of study

Four herbal drugs used in the folk medicine of Central America to treat inflammatory skin affections (Acacia cornigera bark, Byrsonima crassifolia bark, Sphagneticola trilobata leaves and Sweetia panamensis bark) were evaluated for their topical anti-inflammatory activity.

Materials and methods

Petroleum ether, chloroform and methanol extracts were obtained for herbal medicines and then extracts were tested on Croton oil-induced ear dermatitis model in mice.

Results

Almost all the extracts reduced the Croton oil-induced ear dermatitis in mice and the chloroform ones showed the highest activity, with ID₅₀ (dose giving 50% oedema inhibition) values ranging from 112 μg/cm² (Byrsonima crassifolia) to 183 μg/cm² (Sphagneticola trilobata). As reference, ID₅₀ of the non-steroidal anti-inflammatory drug indomethacin was 93 μg/cm².

Conclusions

Lipophilic extracts from these species can be regarded as potential sources of anti-inflammatory principles.     

Leucas cephalotes regulates carbohydrate and lipid metabolism and improves antioxidant status in IDDM and NIDDM rats

Ethnopharmacological relevance

Leucas cephalotes (Roth.) Spreng. (Laminaceae) is an ayurvedic traditional medicinal plant used in India, Nepal and Pakistan to treat several ailments including diabetes.

Aim of the study

The aim of the present study is to investigate the antidiabetic, antihyperlipaemic and antioxidant activities of Leucas cephalotes for its purported use in diabetes.

Materials and methods

The ethanol extract of leaves of Leucas cephalotes was administered (150, 300 and 450 mg kg⁻¹ bw) to diabetes induced (IDDM and NIDDM) rats and carbohydrate, lipid, antioxidant, urea and creatinine profiles were assessed.

Results

All the three doses of extract decreased plasma glucose and lipid profiles and, improved the antioxidant status of both types of diabetic rats. The extract administration improved hepatic glycogen content and hexokinase activity, decreased glucose-6-phosphatase activity, blood urea, creatinine contents and decreased lipid peroxidation in diabetic rats. Of the three doses used, 450 mg kg⁻¹ bw dose was found to be more potent in its effects comparable to those of glibenclamide and metformin.

Conclusion

Leucas cephalotes regulates both carbohydrate and lipid metabolism and, improves body antioxidant defense systems in both types of diabetes.     

Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells

Ethnopharmacological relevance

Astragaloside IV is the primary pure saponin isolated from Astragalus membranaceus, one of the valuable traditional medical herbs. Antifibrotic activities of Astragalus membranaceus have been extensively proved.

Aim of the study

To investigate the effects of astragaloside IV on hepatic stellate cells (HSCs) and hepatic fibrosis in rats induced by porcine-serum (PS).

Materials and methods

Liver fibrosis was induced by PS injection (0.5 ml, twice a week) for 12 weeks. Astragaloside IV (2.0, 4.0 mg kg⁻¹) was administered intragastrically. Liver samples were subjected to histological and immunohistochemical studies. In vitro effects of astragaloside IV on primary cultured HSCs were detected by incorporation assays.

Results

Astragaloside IV delayed the formation of liver fibrosis and decrease the serum levels of hyaluronic acid (HA), procollagen type III (PCIII) and hydroxyproline (Hyp) content in liver. The levels of transforming growth factor-β₁ (TGF-β₁) in serum and expression in liver were significantly decreased by astragaloside IV. Collagen synthesis and proliferation were significantly inhibited by astragaloside IV (1.5, 3.0, 6.0, 12.0 and 24.0 mg L⁻¹) in HSCs.

Conclusion

The results showed that astragaloside IV displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its inhibitory effects on collagen synthesis and proliferation in HSCs.     

Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): A comparative in vitro study with the effects of caffeic and ferulic acids

Ethnopharmacological relevance

In Eurasia folk medicine, roots of chicory (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has been shown to increase insulin secretion by pancreatic β-cells and glucose uptake by muscle cells.

Materials and methods

In vitro experiments were designed to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids, to those obtained with NCRAE (50 and 100 µg.mL⁻¹) on the three major tissues implicated in glycemic regulation (pancreas, muscle and liver). In vivo experiments were performed in Wistar rats submitted to a daily intraperitoneal injection of NCRAE (3, 15 or 30 mg kg⁻¹) for 4 days. On the fourth day, an intraperitoneal glucose tolerance test (IPGTT; 1 g kg⁻¹) was carried out.

Results

Our results show that the three compounds we used are able each to induce an original response. Caffeic acid mainly promotes a decrease in hepatic glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a reduction of hepatic glycogenolysis. However, this compound induces an inhibition of muscle glucose uptake. NCRAE provokes an increase of insulin release and glucose uptake without any effect on hepatic glycogenolysis. We could also show that none of these compounds implicates hepatic glucose 6-phosphatase in contrast to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is able to decrease glucose output from hepatocytes. Our results point out that NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve IP glucose tolerance in a dose-dependent manner and mainly via an insulin sensitizing effect.

Conclusions

We conclude that NCRAE presents an antihyperglycemic effect essentially due to a peripheral effect on muscle glucose uptake.     

Macrophage immunomodulatory activity of the polysaccharides from the roots of Bupleurum smithii var. parvifolium

Aim of the study

Radix Bupleuri, one of the most frequently prescribed crude herbs in traditional Chinese medicine, has been used for centuries to treat inflammatory diseases. However, little is known about the therapeutic mechanisms of crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium. Macrophages play important roles in inflammatory diseases such as systemic lupus erythematosus (SLE). The purpose of the present work was to investigate immunomodulative effects of Bupleurum polysaccharides on murine peritoneal macrophages.

Materials and methods

BALB/c mice were administered intragastrically with Bupleurum polysaccharides 20, 40, and 80 mg kg⁻¹ day⁻¹, or prednisone 3 mg kg⁻¹ day⁻¹ or levamisole 25 mg kg⁻¹ day⁻¹ from day 0 to day 6. Peritoneal macrophages were isolated 5 days after intraperitoneal injection of 1 mL 5% sodium thioglycollate. Phagocytic functions of macrophages were studied; cytokines concentrations in the culture supernatants were determined by enzyme-linked immunosorbent assay and the secretion of nitric oxide (NO) was quantified by Griess reaction.

Results

Treatment with BPs enhanced phagocytic functions of macrophages (phagocytosis of apoptotic thymocytes, IgG-opsonized sheep red blood cells and chicken red blood cells) and inhibited LPS-induced productions of NO and proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).

Conclusions

Bupleurum polysaccharides up-regulated phagocytic activities but inhibited LPS-induced productions of proinflammatory mediators. These data suggested that at least part of the traditional beneficial effects of Bupleurum on inflammatory diseases could be ascribed to the immunomodulatory effects of Bupleurum polysaccharides on macrophages.     

Pharmacokinetics of artemisinin delivered by oral consumption of Artemisia annua dried leaves in healthy vs. Plasmodium chabaudi-infected mice

Ethnopharmacological relevance

The Chinese have used Artemisia annua as a tea infusion to treat fever for >2000 years. The active component is artemisinin. Previously we showed that when compared to mice fed an equal amount of pure artemisinin, a single oral dose of dried leaves of Artemisia annua (pACT) delivered to Plasmodium chabaudi-infected mice reduced parasitemia at least fivefold. Dried leaves also delivered >40 times more artemisinin in the blood with no toxicity. The pharmacokinetics (PK) of artemisinin delivered from dried plant material has not been adequately studied.

Materials and methods

Healthy and Plasmodium chabaudi-infected mice were oral gavaged with pACT to deliver a 100 mg kg⁻¹ body weight dose of artemisinin. Concentrations of serum artemisinin and one of its liver metabolites, deoxyartemisinin, were measured over two hours by GCMS.

Results

The first order elimination rate constant for artemisinin in pACT-treated healthy mice was estimated to be 0.80 h⁻¹ with an elimination half-life (T_½) of 51.6 min. The first order absorption rate constant was estimated at 1.39 h⁻¹. C_max and T_max were 4.33 mg L⁻¹ and 60 min, respectively. The area under the curve (AUC) was 299.5 mg min L⁻¹. In contrast, the AUC for pACT-treated infected mice was significantly greater at 435.6 mg min L⁻¹. Metabolism of artemisinin to deoxyartemisinin was suppressed in infected mice over the period of observation. Serum levels of artemisinin in the infected mice continued to rise over the 120 min of the study period, and as a result, the T_½ was not determined; the C_max and T_max were estimated at ≥6.64 mg L⁻¹ and ≥120 min, respectively. Groups of healthy mice were also fed either artemisinin or artemisinin mixed in mouse chow. When compared at 60 min, artemisinin was undetectable in the serum of mice fed 100 mg AN kg⁻¹ body weight. When plant material was present either as mouse chow or Artemisia annua pACT, artemisinin levels in the serum rose to 2.44 and 4.32 mg L⁻¹, respectively, indicating that the presence of the plant matrix, even that of mouse chow, had a positive impact on the appearance of artemisinin in the blood.

Conclusions

These results showed that artemisinin and one of its drug metabolites were processed differently in healthy and infected mice. The results have implications for possible therapeutic use of pACT in treating malaria and other artemisinin-susceptible diseases.     

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae)

Ethnopharmacological relevance

Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats.

Material and methods

The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H₂O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na⁺, K⁺, Cl⁻ and HCO₃⁻ were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined.

Results

Water and Na⁺ excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2′,5′-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment.

Conclusion

The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway.     

Topical analgesic,anti-inflammatory and antioxidant properties of Oxybaphus nyctagineus: Phytochemical characterization of active fractions

Ethnopharmacological relevance

Oxybaphus nyctagineus (Michx.) Sweet has traditionally been used by several Native American tribes predominantly as a topical anti-inflammatory and analgesic agent.

Aim of the study

To evaluate the antioxidant, analgesic and anti-inflammatory activity of the extracts prepared from the aerial parts of Oxybaphus nyctagineus and to characterize the major chemical constituents of the bioactive extracts.

Materials and methods

Crude polar and apolar extracts (PCE and ACE) of the herb of Oxybaphus nyctagineus were prepared and tested in the models of the CFA-induced hyperalgesia in rat knee and carrageenan-induced paw edema in rat. To identify the active compounds, subfractions were prepared by column chromatography and subjected in vitro assays, such as antioxidant assays (DPPH, peroxynitrite (ONOO⁻) scavenging), and the LPS-induced IL-1β release test in human monocytes. Preparative HPLC was employed for the isolation of active substances, while phytochemical analysis was performed by mean of LC–MS/MS and NMR.

Results

The topically administered PCE and ACE of Oxybaphus nyctagineus demonstrated a significant analgesic and anti-inflammatory effect in the inflammation animal models. The subfraction A4 of ACE and the subfraction P5 of PCE considerably inhibited the LPS-induced IL-1β release in human monocytes, while the strongest activity was localized in the subfraction P5 in the antioxidant assays. The HPLC–MS/MS and NMR analysis revealed that 6-methoxyflavonol diglycosides, namely patuletin-3-O-robinobioside (1), 6-methoxykaempferol-3-O-robinobioside (2), spinacetin-3-O-robinobioside (3), and hydroxy-polyenoic fatty acids, namely corchorifatty acid B (4), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOT acid) (5), and 9-hydroxy-10E,12Z-octadecadienoic acid (9-HOD acid) (6) were present in PCE, and in ACE as major compounds.

Conclusion

The results of this study established a pharmacological evidence for the traditional use of Oxybaphus nyctagineus as an anti-inflammatory agent used topically, and provided data on its phytochemical composition for the first time.     

In vitro antimicrobial activity of Caesalpinia ferrea Martius fruits against oral pathogens

Aim

In the Amazon region of Brazil, the fruits of Caesalpinia ferrea Martius (Brazilian ironwood) are widely used as an antimicrobial and healing medicine in many situations including oral infections. This study aimed to evaluate the antimicrobial activity of Caesalpinia ferrea Martius fruit extract against oral pathogens.

Materials and methods

Polyphenols estimation and spectral analysis (¹H NMR) of the methanol extract were carried out. The microorganisms Candida albicans, Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis and Lactobacillus casei were tested using the microdilution method for planktonic cells (MIC) and a multispecies biofilm model. Chlorhexidine was used as positive control.

Results

Polyphenols in the extract were estimated at 7.3% and ¹H NMR analysis revealed hydroxy phenols and methoxilated compounds. MIC values for Candida albicans, Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis and Lactobacillus casei were 25.0, 40.0, 66.0, 100.0, 66.0 μg/mL, respectively. For the biofilm assay, chlorhexidine and plant extract showed no growth at 10⁻⁴ and 10⁻⁵ microbial dilution, respectively. At 10⁻⁴ and 10⁻⁵ the growth values (mean ± SD) of the negative controls (DMSO and saline solution) for Streptococcus mutans, Streptococcus sp. and Candida albicans were 8.1 ± 0.7, 7.0 ± 0.6 and 5.9 ± 0.9 × 10⁶ CFU, respectively.

Conclusion

Caesalpinia ferrea fruit extract can inhibit in vitro growth of oral pathogens in planktonic and biofilm models supporting its use for oral infections.     

Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia Haw. (Cactaceae)

Ethnopharmacological relevance

Pereskia grandifolia Haw. (Cactaceae), popularly known as “ora-pro-nobis” is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action.

Materials and methods

The infusions (2.5–10%) and the HEPG (3–100 mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na⁺, K⁺, Cl⁻ and HCO₃⁻ were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V₂ vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined.

Results

Water excretion rate was significantly increased by HEPG, while the urinary K⁺ and Cl⁻ excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30 mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment.

Conclusion

The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release.     

The hepatoprotective effect and chemical constituents of total iridoids and xanthones extracted from Swertia mussotii Franch

Ethnopharmacological relevance

Total iridoids and xanthones (TIXS) were extracted from Swertia mussotii Franch, one of the most important eight Tibetan medicines in China, which was recorded in the book of Jingzhu Bencao and used for clinical treatment of cholestatic hepatitis for many years. Our aim was to study the hepatoprotective effect and chemical constituents of the TIXS.

Materials and methods

Crude extracts were prepared using 90% ethanol, and individual fractions were collected following HPD-300 macroporous resin column chromatography. HPLC/MS was applied to qualitatively and quantitatively analyze the TIXS. Then, the alpha-naphthylisot hiocyanate-induced liver damage model was used to assess the hepatoprotective effect of the TIXS.

Results

A total of 12 compounds were identified by the fingerprint chromatography of the TIXS, and swertiamarin and swertianolin were shown to be its two main components. Oral administration of the TIXS at a dose of 35, 70 or 140 mg kg⁻¹, swertiamarin at a dose of 20 mg kg⁻¹ or swertianolin at a dose of 20 mg kg⁻¹, for 7 days in mice significantly reduced the alpha-naphthylisot hiocyanate-induced levels of alanine aminotransferase, aspartate aminotransferase and the total and direct bilirubins, and increased the bile flow (P<0.01).

Conclusion

These findings suggest that the TIXS exhibits significant hepatoprotective effect in the liver damage model induced by alpha-naphthylisot hiocyanate. Its active constituents include swertiamarin and swertianolin.     

Paeonol,the main active principles of Paeonia moutan, ameliorates alcoholic steatohepatitis in mice

Aim of study

Paeonol, a major phenolic component of Moutan Cortex, is traditionally used as a Chinese herbal medicine in various diseases including hepatitis. Evidence shows that paeonol has anti-inflammatory, anti-tumor, and anti-atherosclerosis effects. However, the effect of paeonol on alcoholic liver injury remains obscure. The present investigation was designed to determine the effects of paeonol on alcohol-induced hepatic injury in mice.

Materials and methods

The degree of alcoholic liver injury was evaluated biochemically by measuring serum markers and pathological examination. Real-time PCR and ELISA methods were used to check the expression of cytokines. Western blotting was used to check CYP 450 expression.

Results

Treatment with paeonol significantly attenuated the level of serum aminotransferase, reduced the severe extent of hepatic cell damage, steatosis, and the infiltration of inflammatory cells in a model of alcoholic liver injury (P < 0.05). Interestingly, paeonol markedly decreased hepatic mRNA expression of lipogenic genes (P < 0.05) while had no effect on protein expression of hepatic CYP2E1. Furthermore, paeonol significantly decreased serum and tissue inflammatory cytokine levels, tissue lipid peroxidation, neutrophil infiltration and inhibited the apoptosis of hepatocytes (P < 0.05). Kupffer cells isolated from ethanol-fed mice produced high amounts of tumor necrosis factor alpha, whereas Kupffer cells from paeonol treatment ethanol-fed mice produced less tumor necrosis factor alpha (P < 0.05).

Conclusions

These findings suggest that paeonol may represent a novel, protective strategy against alcoholic liver injury by attenuating hepatic steatosis, inflammatory response and apoptosis.     

Augmentation of expression of immunocytes’ functions by seed extract of Ziziphus mauritiana (Lamk.)

Aim of the study

The present study was carried out to evaluate the immunomodulatory potential of Ziziphus mauritiana (Lamk.) seed extract to ascertain the folkloric claim as immunomodulator.

Materials and methods

The aqueous-ethanolic seed extract (100–400 mg kg⁻¹) of Z. mauritiana was investigated for immunomodulatory potential in mice. The extract was standardized with HPLC using betulinic acid as a marker. Functions of various immunocytes in the form of humoral (development of anti-SRBC (sheep red blood cells) antibody titers) and cell-mediated immune response (delayed type hypersensitivity, nitroblue tetrazolium reduction, inducible nitric oxide synthase activity and bactericidal activity) was studied in SRBC immunized mice. The cytokine, IFN-γ (interferon-gamma) and IL-4 (interleukin-4) secretion was also measured quantitatively by ELISA as the expression of functions of Th-1 and Th-2 respectively. Levamisole (2.5 mg kg⁻¹) was used as standard drug.

Results

The seed extract demonstrated significant (P < 0.05–0.001) up-regulation of cell-mediated, humoral immune response and Th-1 mediated cytokine IFN-γ and decline in Th-2 mediated cytokine IL-4. At higher dose of extract the results were comparable to that of the levamisole.

Conclusion

The immunostimulatory potential of this seed extract is likely to be mediated through its effect on macrophage function and Th-1 mediated immunity confirming the folkloric use of this plant.