Laxative Effect Research Articles

Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice.

Lactobacillus plantarum PS128 has been reported as a psychobiotic to improve mental health through the gut–brain axis in experimental animal models. To explore its mechanism of action in the gut, this study aimed to analyze the effects of L. plantarum PS128 ingestion on naïve and loperamide (Lop)-induced constipation mice. We found that, in the two mouse models, the weight, number, and water content of feces in the L. plantarum PS128 group were higher than those in the vehicle control group. Histological observation revealed that L. plantarum PS128 increased the level of colonic mucins including the major mucin MUC2. In addition, the charcoal meal test showed that L. plantarum PS128 significantly increased the small intestine transit in naïve mice, but not in the Lop-treated mice. Since intestinal serotonin has been found to modulate motility, we further analyzed the expression of genes related to serotonin signal transduction in the small intestine of naïve mice. The results showed that L. plantarum PS128 significantly altered the expression levels of Tph1, Chga, Slc6a4, and Htr4, but did not affect the expression levels of Tph2, Htr3a, and Maoa. Furthermore, immunohistochemistry revealed that L. plantarum PS128 significantly increased the number of serotonin-containing intestinal cells in mice. Taken together, our results suggest that L. plantarum PS128 could promote intestinal motility, mucin production, and serotonin signal transduction, leading to a laxative effect in mice.

STUDY ON EXTRACTION AND PURIFICATION OF TRANS-RESVERATROL FROM VINE WASTE - A REVIEW

Resveratrol (3, 4', 5-trihydroxystilbene) is a natural phenolic compound synthesized by plants in response to various stressful circumstances (mechanical injury, siege of bacteria or fungi and UV exposure). Commercial resveratrol supplements on the market are mostly extracted from Japanese knotweed. As it grows even in heavily polluted environments and the presence of emodin, which is a compound that may have laxative effects and is found in partially purified extracts, additional concerns about the safety of these commercial preparations were raised. An alternative source of resveratrol intensely studied in recent years is vine waste, with recent studies showing high concentrations of resveratrol in extracts. In the last years, the researcher’s attention is focused on obtaining an efficient method of extraction and purification of this compound from the vine waste to show that this material can be used as a raw material for production of commercial supplements of resveratrol.

Laxative activity of Ethanolic extract of Capparis moonii W. fruit.

The growing value as potential preventive interventions of biologically active medicinal plants and their constituents has been a topic of intense research. Plant and plant derivatives have long been a source of medication in human culture. According to world health organizations, 80% of the population of developing countries relies for their primary health treatment on conventional medicines. In the future, safe and effective drugs are likely to be manufactured from medicinal plants to heal multiple degenerative diseases. Constipation has been identified as one of the daily health issues which has recently been increased due to increased intake of processed foods or foods deficient in natural dietary fibres. The present research was carried out to evaluate the laxative effects of ethanolic extract of Capparis moonii wight fruit was safe for administration in mice at the highest dose (2000mg/kg) tested. The Capparis moonii wight’s laxative activity was studied in mice. The result showed that an oral administration of Capparis moonii wight fruit extract produced a significant and dose-dependent increase in stool count in mice, as well as a dosedependent effect through distance traveled by charcoal meal. These effects were comparable with dulcoflex (bisacodyl) (standard drug) at dose of 5mg/kg. From the result it can be concluded that oral administration of Capparis moonii wight ethanolic extract indicates significant laxative activity in mice It can be reported that flavonoid, saponin, glycoside present in the extract may be responsible for an laxative effect and Thus the plant extract can explain the usefulness of Capparis moonii in constipation.

Pharmacological Potential of Sweet Violet (Banafsha) on Human Body

Sweet violet commonly known as Gul-e-Bafasha or Banafsha is a herb widely used as ethnomedicine in dried form in Pakistan for the treatment of various disease or symptoms. Viola odorata had phytochemicals constituents (flavonoids, flavanols, ascorbic acid, phenolics) and antioxidative property Objective: The goal of this research is to emphasize Viola Odorat's (Gul-e-Banafsha) therapeutic benefits on human health. Methods: This review literature is assessed from the previous data available from google scholar, Medline and PubMed. After going through the published articles, researches and literature, initially 104 articles were included, after excluding irrelevant and repeated articles, 37-full text articles and abstract were relevant and found eligible for the study. Results: Sweet violet scientifically known as Viola odorata has been widely used as ethnomedicine in rural areas of Pakistan for the treatment of skin infection, insomnia, inflammation, cough, fever and Cardio Vascular Diseases (CVD) with very low adverse side effects. Its leaves are used as antiseptic used as ointment and its flower has a laxative effect. It is rich in flavonoids like widely known for its therapeutic properties. Due to its phenolic property, it had antioxidant and antimicrobial property, presences of flavonoids had an anti-cancerous effect, it had tannins which reduces the mutagenic activity and it had saponins which reduces blood glucose levels in body. Presence of saponins in Sweet violet lead to the anticarcinogens, melanogenesis, neuroprotective, antimicrobial and anti-inflammatory property. Presence of Isoquinoline alkaloids constituent led to expectorant and antipyretic effect. Viola odorata is used as phytopharmaceuticals and nutraceutical agent. Conclusions: Sweet Voila had acclaimed the therapeutic effect on human health as antiseptic, antifungal, anti-inflammatory, antioxidant, antilipidemic and hepatoprotective activity due to the presences of phenolics, flavonoids, tannins, saponins, alkaloids and coumarins.

Study of laxative and hepatoprotective activity of extracts obtained from Prunus domestica fruits

The experimental work focused on the study of the pharmacological properties of extracts obtained from the Prunus domestica fruits to create a prospective laxative drug with moderate hepatoprotective properties. Prunus domestica fruit extracts have been shown to have a pronounced laxative and moderate hepatoprotective effect. Extract containing fibers at a dose of 200 mg/kg was selected as the most active extract for laxative and hepatoprotective activity among all extracts from the Prunus domestica fruits. It was conventionally named “Prunophyte”. Studies of the specific pharmacological action of “Prunophyte” extract in a model of comorbid functional constipation on the background of combined alcoholic liver disease in rats showed that “Prunophyte” at a dose of 200 mg/kg had positive dynamics in the treatment of constipation on the background of subacute liver disease. In some cases it exceeded the effects of combination therapy with drugs “Silibor” at a dose of 25 mg/kg and “Senadexin” at a dose of 14 mg/kg. “Prunophyte” extract, in contrast to “Senodexin”, did not cause signs of diarrhea in animals, which may be a beneficial feature of this drug in subsequent clinical use. This drug has shown that it can be a promising alternative to a one-time complex treatment with herbal laxatives and hepatoprotectors, which will avoid polypragmatism in the treatment of comorbid conditions in gastroenterology associated with functional constipation and liver dysfunction.

Metabolites Profiling, In Vitro, In Vivo, Computational Pharmacokinetics and Biological Predictions of Aloe perryi Resins Methanolic Extract.

Background: Aloe perryi is a traditional herb that has various biological and pharmacological properties such as anti-inflammatory, laxative, antiviral, antidiabetic, and antitumor effects, which have not been deliberated before. The current investigation aims to evaluate in vitro cytotoxicity against several cancer cell lines in addition to in vivo anti-inflammatory activities of Aloe perryi extract using a rat animal model. Moreover, the pharmacokinetic properties of bioactive constituents and possible biological targets were assessed and evaluated. The methanolic extract of Aloe perryi was prepared by maceration, to tentatively identify the biomolecules of the Aloe perryi extract, analytical LC–QTOF-MS method was employed for Aloe perryi methanolic extract. The cytotoxic activity was examined in six cancer cell lines using Titer-Glo assay and the IC50s were calculated in addition to in silico target predictions and in vivo anti-inflammatory activity assessment. Subsequently, the pharmacokinetics of the identified active components of Aloe perryi were predicted using SwissADME, and target prediction using the Molinspiration webserver. The cytotoxic activity on HL60 and MDA-MB-231 was moderately affected by the Aloe perryi extract with IC50 of 63.81, and 89.85 μg/mL, respectively, with no activity on other cells lines. Moreover, the Aloe perryi extract exhibited a significant increase in wound contraction, hair growth, and complete re-epithelization when compared with the negative control. The pharmacokinetic properties of the bioactive constituents suggested a good pharmaceutical profile for the active compounds and nuclear receptors and enzymes were the two main possible targets for these active compounds. Our results demonstrated the promising activity of Aloe perryi extract with cytotoxic and anti-inflammatory properties, indicating a potential therapeutic utility of this plant in various disease conditions.

The effect of Hylocereus polyrhizus (red dragon fruit) on whole gut transit time of young Malaysian adults

Introduction: The red dragon fruit (Hylocereus polyrhizus) is a popular fruit, not only where it originated from, in Central America, but across the world including in Asia. It contains healthy minerals, vitamins and antioxidants, and has been shown to have gut motility action in animals. Methods: To determine the effect of red dragon fruit on whole gut transit time, a cross-sectional study of whole gut transit time using two different stool markers was conducted among 128 young Malaysian adults. Results: Red dragon fruit, in a half fruit serving of 225±25 grams, reduced mean whole gut transit time from 26.0±12.9 hours to 21.9±12.8 hours (p<0.001) when colour change in stools was used as an indicator. The tests also showed that 14.8-17.3% of individuals had whole gut transit time ≥40 hours with carbon as a stool marker compared to only 7.8-8.6% when red dragon fruit was consumed and used as a marker. Conclusion: This study demonstrated a laxative effect of red dragon fruit among young adults.

THE ANTIOBESITY ACTIVITY OF ETHANOL EXTRACT OF ROSE APPLE (Syzygium jambos (L.) Alston) ON FEMALE WISTAR RATS

<p>Obesity prevalence has increased in recent years and has caused serious health problems. This research was carried out to obtain alternative antiobesity therapy with more minimal side effects. Antiobesity activity of rose apple (Syzygium jambos (L.) Alston) leaves on female Wistar rats induced by high carbohydrate food for 45 days and subcutaneously injection of MSG 2 g/kgbw. Extraction was carried out using maceration method 96% ethanol. The test parameters observed were body weight, food intake, stool consistency and weight, liver and abdominal fat tissue weight. The results showed that high carbohydrate food and monosodium glutamate could induce obesity. Ethanol extract of rose apple leaves at doses of 25, 50 and 100 mg/kgbw body weight had antiobesity activity by inhibiting body weight gain significantly compased to positive control group (p<0.05). The highest antiobesity effect was shown by the ethanol extract of rose apple leaves at a doses of 50 mg/kgbw with % inhibition of body weight gain of 169.3% to positive control group. Ethanol extract of rose apple leaves may reduce appetite, but didn’t have laxative effect and couldn’t reduce fat deposits in the liver and abdominal fat tissue.</p>

Loperamide로 유도된 변비 마우스 모델에서 참모자반(Sargassum fulvellum)의장 기능 개선 효능 평가

In this study, we investigated laxative effects of Sargassum fulvellum (S. fulvellum, SF) on loperamide-induced constipation in mice. First, the hot water extracts of SF (SFH) showed higher carbohydrate contents (26.65 ± 0.53%) than protein (9.41 ± 0.31%) and phenol (2.82 ± 0.00%). Oral administration of SFH effectively increased the body weight and the food intake decreased by loperamide intake in mice. Also, SFH improved the intestinal function by significantly increasing the number, weight and moisture contents of fecal pellets in loperamide-treated mice. Taken together, these results indicated that SFH has laxative effects on loperamide-induced constipation in mice and it might be used as a natural food material for improving or preventing constipation.

Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation.

BackgroundBisacodyl is a member of the diphenylmethane family and is considered to be a stimulant laxative. It has a dual prokinetic and secretory action and needs to be converted into the active metabolite bis‐(p‐hydroxyphenyl)‐pyridyl‐2‐methane (BHPM) in the gut to achieve the desired laxative effect. Bisacodyl acts locally in the large bowel by directly enhancing the motility, reducing transit time, and increasing the water content of the stool. A recent network meta‐analysis concluded that bisacodyl showed similar efficacy to prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, and sodium picosulfate for the primary endpoint of ≥3 complete spontaneous bowel movements (CSBM)/week and an increase of ≥1 CSBM/week over baseline. The meta‐analysis also found that bisacodyl may be superior to the other laxatives for the secondary endpoint of change from baseline in the number of spontaneous bowel movements per week in patients with chronic constipation. This observation stimulated the authors to review the available literature on bisacodyl, which has been available on the market since the 1950 s.PurposeThe aim of the current review was to provide an overview of the historic background, structure, function, and mechanism of action of bisacodyl. Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions.

Diuretic and laxative activities of Kandelia candel and Brownlowia tersa in experimental mice

Different fractionated extracts (in ethanol, n-hexane, chloroform, ethyl acetate and water) of two mangrove plants Kandelia candel and Brownlowia tersa have been investigated here for diuretic and laxative bioactivity. In diuretic test, frusemide (5 mg/kbw) was used as standard and the parameters like volume of urine up to 6th hour, pH, density, conductivity and Na+, K+, Cl- contents of collected urine were measured. Ethyl acetate fraction of Kandelia candel showed significant diuretic activity (p<0.001) at 200 mg/kbw and 400 mg/kbw dose compared with control. For aerial parts of Brownlowia tersa, chloroform fraction demonstrated better diuretic activity. Both the active fractions were found to work as loop diuretics. In laxative activity test, bisacodyl (10 mg/kbw) was used as standard and a significant percent increment of fecal output (p<0.0001) was observed for ethyl acetate fraction of Kandelia candel at both the doses. For Brownlowia tersa, the ethyl acetate and water fractions demonstrated significant laxative effect. Phytochemical analysis for both the plants extracts exhibited the presence of carbohydrate, reducing sugar, steroids, saponins, glycosides, tannins, alkaloids, terpenoids and flavonoids etc. Further studies may be carried to isolate and characterize the active compound(s) responsible for the claimed activity.

Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats.

To investigate the role of tannin-enriched extracts of Ecklonia cava (TEE) on the regulation of oxidative balance and laxative activity in chronic constipation, we investigated alterations after exposure to TEE, on constipation phenotypes, muscarinic cholinergic regulation, and oxidative stress responses in the transverse colons of SD rats with loperamide (Lop)-induced constipation. This extract contains high levels of total condensed tannin content (326.5 mg/g), and exhibited high inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. TEE treatment induced significant improvements in reactive oxygen species (ROS) production, superoxide dismutase (SOD) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in primary smooth muscles of rat intestine cells (pRISMCs) and transverse colon of constipation model. Also, Lop+TEE treated groups showed alleviated outcomes for the following: most stool parameters, gastrointestinal transit, and intestine length were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, mucin secretion, water channel expression and gastrointestinal hormones secretion in the transverse colon; expressions of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators on muscarinic cholinergic regulation were significantly recovered. Taken together, these results provide the first evidence that TEE stimulates oxidative stress modulation and muscarinic cholinergic regulation when exerting its laxative effects in chronic constipation models.

Antimicrobial activity of Phyllanthus niruri (Chanka piedra)

Linnaus (Euphorbiaceae) also known as Chanka piedra is widely grown and used throughout the tropical and subtropical countries of the world. In India it is present in the coastal areas. It is an annual herb and field weed having very short life. Phyllanthus comprises of 600-700 species with minor distinguishing features among them. In Indian ayurvedic system, plant extract of is used as a medicine for asthma, bronchitis, anemia, leprosy, etc., As mentioned in the book Charaka Samhita is used as an effective treatment for stimulating liver, improving digestion, to increase appetite and produce laxative effects. is a traditional herb with long-standing Ayurvedic, Chinese and Malay ethnomedical records and antimicrobial activity. Antimicrobial activity refers to the process of killing or inhibiting the disease causing microbes. Methanolic extract of is an effective antibacterial agent to treat bacterial infections since the extract exhibited significant antimicrobial potency. The alcoholic extract of leaves of shows significant antibacterial activity against cariogenic organisms. The anti microbial activity of aqueous extract is found to be more effective than the acetone extract of against pathogens responsible for common infections of skin, respiratory, urinary and gastro-intestinal tracts.

In vivo acute toxicity, laxative and antiulcer effect of the extract of Dryopteris Ramose.

Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.

Diacerein solid dispersion loaded tablets for minimization of drug adverse effects: statistical design, formulation, in vitro, and in vivo evaluation

Diacerein is a BCS class II drug employed in osteoarthritis management. The acid/base hydrolysis of the unabsorbed diacerein in the colon is responsible for its laxative effect. Therefore, this work aimed to enhance the solubility, dissolution, and oral bioavailability of diacerein. Such enhancement means lower doses and fewer gastrointestinal adverse effects. A 41.31.21 full factorial design was adopted to prepare 24 solid dispersion formulae. Solid-state characterization showed the dissolution of diacerein crystals as metastable amorphous or microcrystalline forms in a matrix system that enhanced the drug dissolution. Desirability factor suggested compounding an optimized formula (F1) of Pluronic®F68 with 1:3 drug:carrier ratio using rotavap that showed higher drug solubility (187.61 µg/mL) than drug powder (22.5 µg/mL). It achieved higher dissolution efficiency (4.04-fold) and rate (6.6-fold) as well as 100% release in 2 min. F1 was compressed into tablets recording greater dissolution efficiency (1.24-fold) and rate (12.5-fold) than the marketed product. The prepared tablet accomplished a 2.66-fold enhancement in diacerein bioavailability compared to the marketed product. In conclusion, the formulation of diacerein as solid dispersion loaded tablets could be of added value for the treatment of osteoarthritis in terms of enhanced patient compliance. Solid dispersion is an easy and scalable technique.

Comparing the Effect of a Herbal-based Laxative (Goleghand®) and Polyethylene Glycol on Functional Constipation among Children: A Randomized Controlled Trial.

Objective:This study aimed to evaluate the effectiveness, safety, and document the reported adverse effect of a herbal-based laxative (Goleghand®) for the maintenance treatment of functional constipation in young children.Methods:We conducted a randomized clinical trial from April 2019 to September 2020. Children aged 2–15 years with functional constipation defined according to the Rome IV criteria were eligible for study inclusion. Eligible children were randomly allocated to receive polyethylene glycol (PEG) or Goleghand®. The number and consistency of stools per day, painful defecation, abdominal pain, and fecal incontinence were reported weekly by parents. The statistical analyses were performed by determining means and standard deviations, t-test, Chi-square test, ANOVA repeated measures, and Fisher's exact test, with significance, accepted at the 5% level.Findings:Sixty patients have been enrolled in the study. Parental satisfaction scores did not change significantly in either group or over the follow-up period. Our results showed that the effect of time (P < 0.001) and also the effect of group type (P = 0.01) on the number of fecal defecations was significant. The mean number of defecations increased first and then decreased significantly over time, but this decrease was more significant in the PEG group than in the Goleghand® group (P = 0.001). Furthermore, the effect of time on the fecal consistency score was significant (P = 0.047). The mean score of fecal consistency in both groups decreased over time.Conclusion:Goleghand® was similar in efficacy to PEG for 8 weeks of pediatric functional constipation treatment in this randomized clinical trial. Goleghand® can be considered as a new herbal laxative drug for pediatric functional constipation.

Evaluation of the Anti-constipation Effects of Abdominal Application of Olive Oil Ointment in Children 1-4Years Old: A Pilot Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

With a prevalence of 0.7 to 29.6%, functional constipation (FC) is a common pediatric complaint worldwide. Current therapeutic strategies for FC mainly include prevention and treatment of fecal impaction, by administration of oral laxatives or rectal medications. However, these agents have been reported to have limited efficacy and a number of serious side effects. In traditional Persian medicine, local application of olive oil was used to relieve childhood constipation. In this pilot placebo-controlled, double-blind, randomized clinical trial, the laxative effects of the external use of olive oil ointment in 1- to 4-year-old children with functional constipation were investigated. Forty patients with FC were randomly assigned in olive oil ointment or placebo groups, receiving either an ointment containing 85% olive oil or a comparable placebo or an ointment containing 85% liquid paraffin adjusted to have color and odor similar to those of intervention ointment, twice a day for 4days. Rome III criteria for functional gastrointestinal disorders (FGIDs) were used to identify eligible patients from three hospitals. The primary outcome measure was treatment success, defined as ≥1 spontaneous stools per day, without episodes of fecal impaction at endpoint (day 4). The secondary outcome measure was the frequency of fecal incontinence, abdominal discomfort or flatulence, painful defecation, and dermal irritations (adverse effect). Improvements in stool frequency started from day 1 and continued up to day 4 (end of the study) and were significantly greater in patients receiving olive oil ointment in comparison with placebo group (p<0.05). No adverse effect (including fecal incontinence, painful defecation, gripe and skin reaction, etc.) was reported in intervention and placebo groups during the study. Olive oil ointment used in this study can be presented as a safe, well-tolerated, and effective herbal preparation in children with functional constipation.

A COMPREHENSIVE REVIEW ON FICUS CARICA L. - AN UNEXPLORED MEDICINAL PLANT

Fig is one of the earliest cultivated fruit in human history and an important crop worldwide which can be consumed in both fresh and dry form. The genus Ficus belongs to the Moraceae family and there are thousands of species in the genus Ficus. They are mostly found in tropical and subtropical regions. Figs are extremely nutritious and contain a large amount of minerals, vitamins, dietary fibre, carbohydrates, amino acids and other phytochemicals. F.carica was used as a cure-all in systems of medicine such as Ayurveda, Unani, Siddha, and Homeopathy. Studies revealed that F.carica has antioxidant, antimicrobial, anticancer, anti-mutagenic, anti-angiogenic, anti-inflammatory, antidepressant, antiplatelet, antipyretic, immunological, dermatological, hepatoprotective, antidiabetic, hypolipidemic, nootropic, antispasmodic, antidiarrheal, nephroprotective and laxative effects. Fruit juice of F. carica mixed with honey is used to treat haemorrhage.Thus the review attempts to shed light on all the available literature on the Ficus carica L. with reference to its traditional uses, chemical and phytoconstituents,physicochemical properties, and summing up of its various nutritional and therapeutic benefits.

Comparison of content-toxicity-activity of six ingenane-type diterpenoids between Euphorbia kansui before and after stir-fried with vinegar by using UFLC-MS/MS, zebrafish embryos and HT-29 cells

The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1), 5-O-benzoyl-20-deoxyingenol (2), 20-deoxyingenol (3), 3-O-(2’E,4’E-decadienoyl)-20-O-acetylingenol (4), 20-O-(2’E,4’Z-decadienoyl)ingenol (5), and ingenol (6), in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min−1. Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1, 2, 4, and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC50 > 200 μM). Meanwhile, 1, 2, 4, 5, and 6 significantly increased the expression of AQP3 protein (p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.

Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK activation

BackgroundUlcerative colitis (UC) is a non-specific chronic inflammatory disease. The incidence of UC in China has been increasing in recent years. Mogrol is an aglycone of mogrosides. Studies have shown that mogrosides have anti-oxygenation, anti-inflammatory, and laxative effects as well as other biological activities. PurposeTo investigate the beneficial effects of mogrol on UC and identify its underlying mechanisms. Study designWe used the dextran sodium sulphate (DSS)-induced UC model in mice, TNF-α-damaged NCM460 colonic epithelial cells, macrophage cells THP-M stimulated with lipopolysaccharide (LPS) / adenosine triphosphate (ATP) and compound C (an AMPK inhibitor) to confirm the key role of AMPK (AMP-activated protein kinase) activation. MethodsHistological evaluation, immunohistochemical staining, Western blot analysis, immunofluorescence assay and quantitative real time-PCR were used in the study. ResultsOral administration of mogrol (5 mg/kg/daily) in vivo significantly attenuated pathological colonic damage, inhibited inflammatory infiltration and improved the abnormal expression of NLRP3 inflammasome in colonic mucosa via the AMPK and NF-κB signaling pathways. In vitro, mogrol protected against intestinal epithelial barrier dysfunction by activating AMPK in TNF-α-treated NCM460 cells and inhibited the production of inflammatory mediator in LPS-stimulated THP-M cells. Furthermore, mogrol's effects were reversed by compound C intervention in DSS-induced UC model. ConclusionMogrol exerts protective effects in experimental UC and inhibits production of inflammatory mediators through activation of AMPK-mediated signaling pathways.