Natural Salicylates Research Articles

Risks and benefits of salicylates in food: a narrative review.

Salicylates are generally present in plants as part of their defense system against pathogens and environmental stress. Major dietary sources of salicylates were found in spices and herbs, such as curry and paprika (hot powder). Several studies suggest that these natural salicylates offer health benefits in the human body, such as antidiabetic, anticancer, antiviral, and anti-inflammatory properties. However, despite their advantages, salicylates can be harmful to people with allergies, and high doses of salicylates may cause respiratory alkalosis and gastrointestinal bleeding. Additionally, salicylates can interact with certain drugs, such as nonsteroidal anti-inflammatory drugs and warfarin. This narrative review aimed to consolidate recent information on the content of salicylates in food based on the literature, while also highlighting the benefits and risks associated with salicylate consumption in humans. Based on the literature review and analysis of results, it can be concluded that the dietary intake of salicylates in vegetarians can be relatively high, resulting in concentrations of salicylic acid in the blood and urine that are comparable to those observed in patients taking a low dose of aspirin (75 mg). This suggests that a diet rich in salicylates may have potential benefits in preventing and treating some diseases that require low doses of aspirin.

Impact of Selected Eicosanoids in Normal and Pathological Pregnancies.

Pregnancy is a physiological state in which the female body undergoes a series of changes and adaptations to provide the best possible conditions for the growth and development of the forming baby. The internal adaptations that take place lead to the production of inflammation, which is necessary for the initial and final stages of pregnancy (embryo implantation and induction of labor). Gestational diabetes mellitus is considered to be the most common pathology during this period. However, many more serious health complications can arise, which include pre-eclampsia, fetal stunting, and preterm labor. The purpose of this study was to analyze the impact of the levels of individual eicosanoids on the course of normal pregnancy and the possibility of pathologies including gestational diabetes and pre-eclampsia. Sixty-nine pregnant women who were overweight or obese before and during pregnancy were studied. Eicosanoids were extracted as appropriate and then determined using liquid chromatography. The levels of eicosanoids studied in pregnant women differed not only according to the week of pregnancy but also in relation to individual anthropometric and biochemical parameters. There was a significant correlation between being overweight and having a high BMI before pregnancy-as well as biochemical parameters of lipid and carbohydrate profiles-and the occurrence of pathological conditions in pregnancy. Eicosanoids are involved in the pathology of pregnancy associated with the occurrence of gestational diabetes and pre-eclampsia. Salicylic acid may find use in the treatment of pregnant women exposed to both phenomena, as well as in overweight and obese women found before pregnancy. Diets rich in natural salicylates, methods of administration, and pharmacotherapy and dosage need further study. Some of the mediators (lipoxin, prostaglandin and leucotrien) may be new diagnostic markers in pregnancy pathology and intervention pathways in the future.

Natural Salicylates and Their Roles in Human Health.

Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses. Increasing reports suggest that this phenolic compound and its derivatives, collectively termed salicylates, not only regulate plant defense but also have beneficial effects on human health. Both natural and synthetic salicylates are known to have multiple targets in humans, thereby exhibiting various appreciating pharmacological roles, including anti-inflammatory, anticancer, neuroprotective, antidiabetic effects, and so on. The role of some salicylates, such as acetylsalicylic acid (aspirin), 5-aminosalicylic acid (mesalazine), and amorfrutins in human diseases has been well studied in vitro. However, their clinical significance in different diseases is largely unknown. Based on recent studies, five natural salicylates, including amorfrutin, ginkgolic acid, grifolic acid, tetrahydrocannabinolic acid, and cannabidiolic acid, showed potential roles in different challenging human diseases. This review summarizes together some of the recent information on multitarget regulatory activities of these natural salicylates and their pharmacological roles in human health.

Preclinical pharmacokinetic evaluation and metabolites identification of methyl salicylate-2-O-β-d-lactoside in rats using LC–MS/MS and Q-TOF-MS methods

Methyl salicylate-2-O-β-d-lactoside (MSL) is a natural salicylate derivative from the traditional Chinese medicine of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis). As a non-steroidal anti-inflammatory drug (NSAID), MSL exerts a significant anti-arthritis effect but hardly has any gastrointestinal toxicity. In this paper, the pharmacokinetics, distribution, excretion and identification of MSL and its metabolites are described following rat oral and intravenous administration. The biological samples were quantified by UPLC–MS/MS and the metabolites in urine and feces were identified by using Q-TOF-MS. These results will support future investigations leading to clinical development of this drug.

Anti-inflammation effect of methyl salicylate 2-O-β-D-lactoside on adjuvant induced-arthritis rats and lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells.

Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway.

Herbal drugs of the local origin with analgesic activity

Pain is a conscious, unpleasant sensory and emotional experience associated with the existing (current) tissue damage. In general, pain is whatever the patient says it hurts. In the literature we can find many definitions of pain, but in life this is really the most uncomfortable feeling that occurs in the body, and therefore is not surprising that the best selling medicine today are drugs with analgesic activity (painkillers). One of the most commonly used conventional painkillers today is aspirin, and the main active substance is acetyl - salicylic acid. Salicylates like substances used to relieve inflammation and pain are more present in the nature than the people know. Natural salicylates rarely cause ulcers and other changes in the digestive tract. However, due to a number of side effects of synthetic painkillers, there is an increase of patients who are turning to traditional methods of treatment. In the nature we can find a large number of medicinal plants that exhibit analgesic effect. They are also a valuable source of substances of natural origin, potential analgesics. However, it should be noted that the use of medicinal plants, as the basis of folk medicine, is not always completely safe and without side effects. Therefore, attention should be directed towards a detailed study of the chemical composition and biological activity of medicinal plants in order to confirm its efficacy and safety of use as analgesics.

Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents--implications for cancer treatment and chemoprevention.

Epigenetic processes and miRNAs have been recognized as new targets for anticancer drug design. However, old multi-target drugs such as aspirin may also target epigenetic processes. This review aims to provide an overview of our current knowledge on the modulation of epigenetic processes by aspirin and other non steroidal anti-inflammatory agents (NSAIDs) and their implications for cancer treatment and chemoprevention. In vitro and in vivo studies, as well as primary patient data, suggest that aspirin and other NSAIDs reverse tumour suppressor gene hypermethylation in cancer tissues. It must be emphasized that, at this point in time, patient data are limited and DNA hypermethylation reversal has been investigated, but not tumour suppressor gene activation. In addition, evidence from experimental and patient data suggests that aspirin and NSAIDs may also reverse global DNA hypomethylation. At the histone level, both induction and inhibition of deacetylases by aspirin have been reported. Also, direct acetylation of histones by aspirin has been reported, while the natural salicylate anacardic acid has been found to inhibit histone acetyltransferase p300 both in vitro and in vivo, and to regulate gene expression through modulation of histone acetylation. Salicylates and other NSAIDs may also down-regulate miRNAs with oncogene-like functions or up-regulate miRNAs with tumour suppressor-like functions. Up till now, clinical trials have been aimed at investigating the effect of salicylates and NSAIDs on a limited number of miRNAs. So, although the existing evidence is still limited, evidence is accumulating that epigenetic targets may represent nodal targets for the anti-proliferative actions of salicylates and NSAIDs. This, in turn, may have implications for cancer chemoprevention and treatment. Undoubtedly, this notion requires further investigation, but if proved correct, it could lead to the design of less toxic agents that target epigenetic processes as part of existing or novel multi-targeted treatment modalities.

Minding the greens: Role of dietary salicylates in common behavioural health conditions

The role of artificial food additives and food chemicals in abetting certain behavioural conditions has been the subject of behavioural nutrition research over several decades. However, a few studies have also raised questions regarding a similar role possibly played by naturally occurring phytochemicals in general and salicylates in particular. Such studies have, however, been rather few and far between. More importantly, till date, there has been no attempt to collate the findings from the few studies that have been carried out at different points in time by different researchers across different countries and cultures. This gap in the extant body of knowledge is made especially prominent by the fact that naturally occurring salicylates abound in many green vegetables and fruit, which are common constituents of a healthy diet. The aim of this review article is two-fold — firstly, to collate and present the related researches on the effects of salicylates in general and natural salicylates in particular on mental health; and secondly, to identify promising research directions for the future.

Salicylate elimination diets in children: is food restriction supported by the evidence?

A review of case notes from our Sydney-based paediatric allergy services, between 1 January 2003 and 31 December 2011, identified 74 children who had been prescribed diets that eliminated foods containing natural salicylates before attending our clinics. The most common indications for starting the diets were eczema (34/74) and behavioural disturbances (17/74) including attention deficit hyperactivity disorder (ADHD). We could find no peer-reviewed evidence to support the efficacy of salicylate elimination diets in managing these diseases. We do not prescribe these diets, and in a survey of European and North American food allergy experts, only 1/23 respondents used a similar diet for eczema, with none of the respondents using salicylate elimination to treat ADHD. A high proportion (31/66) of children suffered adverse outcomes, including nutritional deficiencies and food aversion, with four children developing eating disorders. We could find no published evidence to support the safety of these diets in children. While this uncontrolled study does not prove a causal relationship between salicylate elimination diets and harm, the frequency of adverse events appears high, and in the absence of evidence of safety or efficacy, we cannot recommend the use of these diets in children.

Pharmacokinetics of methyl salicylate‐2‐O‐β‐D‐lactoside, a novel salicylic acid analog isolated from Gaultheria yunnanensis ,in dogs

Methyl salicylate-2-O-β-D-lactoside (MSL), a natural salicylate derivative of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis), has been shown to provide a beneficial anti-inflammatory effect in animal models. Studies on the pharmacokinetics and bioavailability of MSL can provide both a substantial foundation for understanding its mechanism and empirical evidence to support its use in clinical practice. A simple and sensitive high-performance liquid chromatography (HPLC) method, coupled with ultraviolet analyte detection, was developed for determining the concentration of MSL and its metabolite in beagle plasma. Chromatographic separation was achieved on a Agilent Zorbax SB-C18 column (5 μM,4.6 × 250 mm). The mobile phase consisted of aqueous solution containing 0.1% phosphoric acid and acetonitrile (82:90, v/v), at a flow rate of 1 mL/min. Validation of the assay demonstrated that the developed HPLC method was sensitive, accurate and selective for the determination of MSL and its metabolite in dog plasma. After orally administering three doses of MSL, it could no longer be detected in dog plasma and its metabolite, salicylic acid, was detected. Salicylic acid showed a single peak in the plasma concentration-time curves and linear pharmacokinetics following the three oral doses (r(2) > 0.99). In contrast, only MSL was detected in plasma following intravenous administration. These results will aid in understanding the pharmacological significance of MSL. The developed method was successfully used for evaluation of the oral and intravenous pharmacokinetic profile of MSL in dogs.

Salicylate elimination diets in children: is food restriction supported by the evidence?

A review of case notes from our Sydney-based paediatric allergy services, between 1 January 2003 and 31 December 2011, identified 74 children who had been prescribed diets that eliminated foods containing natural salicylates before attending our clinics. The most common indications for starting the diets were eczema (34/74) and behavioural disturbances (17/74) including attention deficit hyperactivity disorder (ADHD). We could find no peer-reviewed evidence to support the efficacy of salicylate elimination diets in managing these diseases. We do not prescribe these diets, and in a survey of European and North American food allergy experts, only 1/23 respondents used a similar diet for eczema, with none of the respondents using salicylate elimination to treat ADHD. A high proportion (31/66) of children suffered adverse outcomes, including nutritional deficiencies and food aversion, with four children developing eating disorders. We could find no published evidence to support the safety of these diets in children. While this uncontrolled study does not prove a causal relationship between salicylate elimination diets and harm, the frequency of adverse events appears high, and in the absence of evidence of safety or efficacy, we cannot recommend the use of these diets in children.

Evaluation of the new anti-inflammatory compound ethyl salicylate 2-O-β-d-glucoside and its possible mechanism of action

Ethyl salicylate 2-O-β-d-glucoside (ESG) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, it has been used for the treatments of rheumatoid arthritis, swelling and pain. The aim of this study was to evaluate the anti-inflammatory effects of ESG and explore the anti-inflammatory mechanisms. We found that ESG had potent anti-inflammatory effects on the lipopolysaccharide (LPS)-activated murine macrophages RAW264.7. ESG exerted a dose-dependent inhibition of the LPS-stimulated release of the pro-inflammatory cytokines TNF-α and IL-1β. Moreover, it significantly inhibited LPS-stimulated the production of NO and PGE2 by repressing the expression of iNOS and COX protein respectively. Western blot analysis showed that ESG prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells by blocking phosphorylation of inhibitor IκBα and p65. Consistent with these results, we found that ESG prevented the nuclear translocation of NF-κB induced by LPS. Our study suggests that ESG may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the NF-κB signal pathway.

Mediterranean diet: Natural salicylates and other secrets of the pyramid

Mediterranean diet (MDT), a traditional dietary model followed by countries of the Mediterranean basin, has recently been included by UNESCO into the intangible cultural heritage of humanity, as a nutritional prototype of worldwide value [1]. MDT exerts a significant anti-inflammatory, cardioprotective and anticancer action, and by these mechanisms guaranties longevity [2,3].

Effectiveness of Restricted Elimination Diets for Management of ADHD: Concerns about the 2011 INCA Study

Study, 1 • Research Findings, 10 For more than 30 years, parents and professionals have been interested in the extent to which symptoms of ADHD may be a result of allergic reactions to artificial colorings, flavorings, or preservatives routinely added to food consumed by children. Ever since physician Benjamin Feingold (1975) asserted that up to 70% of children with ADHD were so as a consequence of such food allergies or sensitivities, substantial research has been undertaken to explore this possibility. Much of this research occurred in the 1970s and early 1980s, most of which was summarized in a book by psychologist C. Keith Conners (1980). Kavale and Forness (1983) conducted the first meta-analysis of 23 studies of Feingold’s Kaiser-Permanente (K-P) diet in which foods containing natural salicylates, artificial colorings, and some preservatives were removed from children’s diets. This review noted an average effect size (ES)* of 0.12 (not significant), with teacher ratings reflecting a slightly greater effect size (0.27). Poorly controlled studies had a somewhat higher ES (0.33) than better controlled studies (0.09). Such ES levels are relatively modest and 3 to 4 times smaller than effects achieved by ADHD medications, so the K-P diet was not a panacea for ADHD and was surely not going to replace other science-based treatments for the disorder. The early reviews concluded that while, at most, a small fraction of children (11–33%), particularly in the preschool age group, may show some increase in ADHD-like symptoms upon exposure to these additives or some reduction in symptoms following their removal, the majority of children were unaffected by such manipulations, including those with ADHD. Thus, there seemed to be some small effect, presumably due to allergic responses, but hardly the extensive and pervasive effects claimed by Feingold. Effectiveness of Restricted Elimination Diets for Management of ADHD: Concerns about the 2011 INCA Study

A genetic journey through cancer: from rarity and family to aspirin and nanowires

Rare diseases illuminate the most important molecular steps along cell pathways. A clinical encounter with a woman crippled by the autosomal dominant turban tumour syndrome or cylindromatosis led us to chromosome 16 and the CYLD gene, later shown to be a key regulator of ubiqitination in the NFkappa B pathway and a potential target for high dose salicylate therapy. A genome wide approach added dysregulated tropomyosin kinase signaling (Trk).We developed an in vitro cylindroma primary cell culture model which permitted experimental validation of Trk inhibitors as a viable therapeutic approach. Familial studies in our centre have focused on hereditary cancer. Two large pedigrees led to collaboration with Kolodner in identification of the mismatch repair pathway and rapid entry into diagnostics which, in turn, led to development in 1994 of our international CAPP2 randomised controlled trial of aspirin and resistant starch in 1009 carriers of an MMR gene defect. We have demonstrated, in prolonged double blind follow up that taking 2 aspirins daily for 2 years results in a subsequent 60% reduction in new cancers at a mean of 5 years (paper in press). COX2 inhibition is an unlikely sole mechanism for such delayed effects. Enhanced apoptosis, similar to that seen in infected plants triggered by natural salicylates, would explain the effect. Another under-explored mechanism open to modulation is the immune response to mismatch repair deficient cells. Lymphocytic infiltration is the hallmark of these tumours and recent studies by our research partners have revealed striking levels of immune response to the frame-shift derived neopeptides released by MMR deficient cells. These antibody responses provide a credible biomarker for our planned CAPP3 dose inferiority study which will examine different doses of aspirin in 3000 gene carriers. This immunological discovery also opens the way to possibility of a vaccine against the neopeptides which would have relevance for the 1 in 6 sporadic cancers which manifest acquired MMR defects. Simpler methods to investigate tumour genomes in the pathology lab are needed because while aspirin can be offered to all, most new therapies call for greater targeting. . Our commercial venture, QuantuMDx hopes to fill this gap. Tethering single strand DNA to a silicon nanowire and sequencing with heavily charged chain terminating nucleotides in a microfluidic vehicle offers robust cheap genotyping “while you wait”, converting chemistry to computer code without the “middlemen”. Affordable and reliable testing for microsatellite instability and activating ras mutations could then be easily incorporated into standard histopathology practice. Proof of principle is anticipated within months and a commercial device is planned within three years. If the method proves to be as robust as we anticipate, it offers cheap genotyping in pharmacies for common variants such as the UGT1A6 polymorphisms which modulate response to aspirin and would allow more personalised dosing as we move towards a recommendation of general aspirin use in the over 50’s for prevention of vascular events and cancer.

A systematic review of salicylates in foods: Estimated daily intake of a Scottish population

Several studies suggest that natural salicylates in plant-based foods may benefit health. However, large variation in published values of the salicylate content of foods means that relating dietary intakes to disease risk is problematical. Consequently, we have systematically reviewed the available literature using prescribed selection criteria. By combining these literature values with in-house analysis, we have constructed a food composition database describing median salicylate values for 27 different types of fruits, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages. Application of a validated food frequency questionnaire estimated median dietary intakes of 4.42 (range 2.90-6.27) and 3.16 (2.35-4.89) mg/day for Scottish males and females, respectively. Major dietary sources of salicylates were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non-alcoholic beverages including fruit juices (13%), tomato-based sauces (12%) and vegetables (9%). Application of the database to populations with differing dietary habits and disease risk profiles may provide further evidence for the role of dietary salicylates in the prevention of chronic diseases.

Natural salicylates: foods, functions and disease prevention

Salicylic acid and related compounds are produced by plants as part of their defence systems against pathogen attack and environmental stress. First identified in myrtle and willow, the medical use of salicylate-rich preparations as anti-inflammatory and antipyretic treatments may date back to the third millennium BC. It is now known that salicylates are widely distributed throughout the plant kingdom, and they are therefore present in plant products of dietary relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid demonstrates several bioactivities that are potentially disease-preventative, including the inhibition of production of potentially neoplastic prostaglandins, which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it appears to be readily absorbed from the food matrix. This has led some to suggestions that the recognised effects of consuming fruit and vegetables on lowering the risk of several diseases may be due, in part, to salicylates in plant-based foods. However, published estimates of daily salicylic acid intake vary markedly, ranging from 0.4 to 200 mg day(-1), so it is unclear whether the Western diet can provide sufficient salicylates to exert a disease-preventative activity. Some ethnic cuisines that are associated with lowered disease risk may contain considerably more salicylic acid than is obtainable from a Western diet. However known protective effects of acetylsalicylic acid (Aspirin™) may have lead to an over-emphasis on the importance of dietary salicylates compared with other bioactive plant phenolics in the diet.

Chronische Urtikaria – rationelle Diagnostik

After the implementation of DRGs, it seemed necessary to review the standardized diagnostic procedures with respect to effectiveness in identifying causes for chronic urticaria in order to reduce contents in a medically and economically meaningful manner. The test findings of 567 patients with chronic urticaria or angioedema hospitalized from 1989 - 2000 in the Department of Dermatology in Niimberg were analyzed retrospectively. The diagnostic procedures consisted of anamnesis, search for focal infections, allergy tests and provocation tests of intolerance reactions. The main emphasis of the study was placed on the intolerance test to ASA. By potato-rice diet - carried out as prerequisite for provocation tests - symptoms ceased in 37.1% of patients and an improvement of symptoms was shown in 10.1%. During intolerance tests, 27.0% of the provoked patients reacted to ASA. The remaining intolerance substances indometacin, paracetamol, food additives and natural salicylates rarely produced an intolerance reaction. Also, administering additive and natural salicylates enriched food provoked only a few intolerance reactions. Rational diagnostic procedures of the chronic urticaria consist of several steps. During the provocation test the potato-rice diet should be carried on because many patients expressed a total elimination of signs after a short time. The provocation test with ASA should be retained because of numerous positive reactions. However, the provocation test with food additives and salicylates and the provocation food do not represent a compelling component in routine diagnostics of chronic urticaria any longer. By uncovering intolerance reaction the causative factors of urticaria is found in a few cases. Therefore, the search for focal infections and autoimmune disorders should always be conducted because chronic urticaria can represent a multifactorial occurrence.

Respiratory symptoms in patients with inflammatory bowel disease and the impact of dietary salicylates

Background Respiratory symptoms are over-represented in inflammatory bowel disease. There are similarities between the epidemiology of inflammatory bowel disease and that of respiratory conditions for which an adverse influence of salicylate has been identified. Natural salicylates exist within our diet. Aims To determine whether a lower intake of dietary salicylates is associated with less active inflammatory bowel disease and fewer concurrent respiratory symptoms. Patients and methods Respiratory status, inflammatory bowel disease activity, quality of life, and dietary habits were established in 73 patients with Crohn's disease and 69 with ulcerative colitis, using a self-administered questionnaire and peak expiratory flow rate readings. Harvey–Bradshaw and Simple Birmingham/Royal Free Colitis indices, an internally validated respiratory score, and estimated weekly dietary salicylate intake, were calculated for each patient. Results There was at least one respiratory symptom in 63.4% of patients. The commonest underlying respiratory diagnosis was asthma. Respiratory impairment was similar in ulcerative colitis and Crohn's disease; 56.3% of Crohn's disease patients with an active respiratory diagnosis had other extra-intestinal manifestations. The dietary salicylate intake was independent of respiratory status, but inversely correlated with ulcerative colitis activity (dietary salicylate intake 37.0 mg versus 21.4 mg for low and higher Simple Birmingham/Royal Free Colitis index, respectively; p < 0.02). A similar association was not seen in Crohn's disease. Conclusions Respiratory impairment is common in inflammatory bowel disease. Higher intake of dietary salicylates is associated with less active colitis and possibly causally so.

Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: Towards a better non-steroidal anti-inflammatory drug

One of the major factors limiting the use of non-steroidal anti-inflammatory drugs is gastrointestinal toxicity. Gaultherin, 2-[(6-O-β- d-Xylopyranosyl-β- d-glucopyranosyl)oxy] benzoic acid methyl ester, a natural salicylate derivative extracted from Gaultheria yunnanensis, has been shown to have analgesic and anti-inflammatory effects and lack gastric ulcerogenic effect compared to aspirin in our primary study. The aim of this study was to investigate the mechanism of action of gaultherin, which may rely on its active metabolite, and the mechanism responsible for the non-ulcerogenic property. The results showed that gaultherin (200 mg/kg) significantly inhibited the abdominal contractions in the acetic acid-induced writhing test in mice. The anti-inflammatory effect of gaultherin was demonstrated in the croton oil-induced ear edema model in mice. The results showed that gaultherin and equimolar dose of aspirin produced comparable inhibitory effects. The study of the metabolism characters of gaultherin in mice and rats indicated that gaultherin could be metabolically converted to salicylate, which produced the pharmacological effects, and provided effective concentrations for an extended period. In vitro metabolism experiment showed that gaultherin was metabolized by β-glycosidase produced by human intestinal bacteria and esterases in intestine, blood and liver successively to release salicylate finally. The study suggested gaultherin did not cause gastric ulcer for the reason that it released salicylate in intestine slowly, not in stomach and it left the cyclooxygenase-1 unaffected, which was the source of cytoprotective prostaglandins in gastric epithelium.