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Abstract

Pain is considered the third most common healthcare problem disabling more individuals than heart disease and cancer together. Although pharmacological pain management offers a significant relief in several pain-related diseases, many patients turn to its supplementation with complementary and alternative medicine. Botanicals used in pain therapy can contribute to restoring the quality of life to a patient and may effect and enhance conventional pain management. Herbal analgesic use in several pain-related diseases such as rheumatologic diseases, back pain, cancer, diabetic peripheral neuropathy and migraine will be discussed. In addition, this review describes botanicals with known analgesic activity for which randomized, placebo-controlled, double-blind trials assessing their efficacy in different pain-related diseases have been published and which have been recently evaluated in many systematic reviews with well-described methodology.

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... Conventional therapies are correlated with several limitations including restricted long-term efficacy, tolerance problems and other adverse effects (Verkamp et al., 2013). These drawbacks have lead to the escalating prevalence of TM as endorsed by various studies (Berman et al., 2009; Bruckenthal, 2010; Rehberg, 2010; Fouladbakhsh et al., 2011; Peleg et al., 2011; Yoon and Kim, 2013; Zareba, 2009; Da Silva et al., 2012; Arome et al., 2014). The use of TM can be linked to a myriad of factors including psycho-social factors, ethnic and cultural characteristics, accessibility to healthcare resources and individual perception of physical and medical conditions (Yoon and Kim, 2013). ...
... The use of TM can be linked to a myriad of factors including psycho-social factors, ethnic and cultural characteristics, accessibility to healthcare resources and individual perception of physical and medical conditions (Yoon and Kim, 2013). One of the most common therapies used for pain management and treatment is herbal remedies (Zareba, 2009; Da Silva et al., 2012; Arome et al., 2014). Indeed, panoply of medicinal plants has been reported to be in common use for the management and treatment of various pain-related conditions . ...
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In this study, seven exotic/indigenous medicinal plants of Mauritius, namely Coix lacryma-jobi (Poaceae), Aegle marmelos (Rutaceae), Artocarpus heterophyllus (Moraceae), Vangueria madagascariensis (Rubiaceae), Azadirachta indica (Meliaceae), Eriobotrya japonica (Rosaceae) and Syzigium cumini (Myrtaceae) were studied for possible effects on starch breakdown by alpha-amylase in vitro. The results showed that only Artocarpus heterophyllus significantly (p < 0.05) inhibited alpha-amylase activity in vitro. To confirm the observed effects, a further biochemical assay was undertaken to investigate the effects of Artocarpus heterophyllus on alpha-amylase activity using rat plasma in vitro. It was found that the aqueous leaf extract significantly (p < 0.05) inhibited alpha-amylase activity in rat plasma. The highest inhibitory activity (27.20 +/- 5.00%) was observed at a concentration of 1000 microg/mL. However, in both cases dose dependency was not observed. Enzyme kinetic studies using the Michaelis-Menten and Lineweaver-Burk equations were performed to establish the type of inhibition involved. In the presence of the plant extract the maximal velocity (Vmax) remained constant (1/150 g / L/s) whereas the Michaelis-Menten constant (Km) increased by 5.79 g / L, indicating that the aqueous leaf extract of Artocarpus heterophyllus behaved as a competitive inhibitor. Results from the present study tend to indicate that Artocarpus heterophyllus could act as a 'starch blocker' thereby reducing post-prandial glucose peaks.
... Conventional therapies are correlated with several limitations including restricted long-term efficacy, tolerance problems and other adverse effects (Verkamp et al., 2013). These drawbacks have lead to the escalating prevalence of TM as endorsed by various studies (Berman et al., 2009;Bruckenthal, 2010;Rehberg, 2010;Fouladbakhsh et al., 2011;Peleg et al., 2011;Yoon and Kim, 2013;Zareba, 2009;Da Silva et al., 2012;Arome et al., 2014). The use of TM can be linked to a myriad of factors including psycho-social factors, ethnic and cultural characteristics, accessibility to healthcare resources and individual perception of physical and medical conditions (Yoon and Kim, 2013). ...
... The use of TM can be linked to a myriad of factors including psycho-social factors, ethnic and cultural characteristics, accessibility to healthcare resources and individual perception of physical and medical conditions (Yoon and Kim, 2013). One of the most common therapies used for pain management and treatment is herbal remedies (Zareba, 2009;Da Silva et al., 2012;Arome et al., 2014). Indeed, panoply of medicinal plants has been reported to be in common use for the management and treatment of various pain-related conditions. ...
... Gabapentin (PO) 100 to 1200 mg 3 times daily. 44 which are similar to the conventional analgesics (Table 6). Readers are encouraged to refer to the relevant reviews and papers for more details. ...
Article
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Introduction: Pain is a common symptom in cancer patients, but very little information about the prevalence, severity, and treatment of pain in cancer patients in Singapore is available. Therefore, our prospective survey in the National Cancer Centre (NCC) outpatients is incorporated in this report. In addition, a review concerning the recent advances on non-interventional pain management in cancer treatment, which is relevant in the context, is discussed. Materials and Methods: For the prospective survey, a questionnaire was distributed for self-administration by patients while waiting for consultation at the NCC outpatient departments. Literature searches on advances in pain management were conducted, reviewed and discussed. Results: In the last decade, there have been advances in pain pharmacology ranging from wider therapeutic options and management approaches to novel delivery techniques. Acupuncture and massage therapy became increasingly popular among cancer patients. Some clinical trials of acupuncture show benefits in palliation of cancer pain. From the prospective survey, 41.2% of the responders reported pain in the past week, and only 70.8% talked to their doctors about their pain. One third of the patients received analgesics. Of these, 86.5% said that they were taking the prescribed medications, however, 37.4% admitted to having difficulties taking them. Non-drug methods were used by 25.4% of the patients. Medicated oil, cream or gel was used by 49.3%; only 2.6% reported use of Chinese herbs. Conclusion: Pain is a significant symptom in outpatients attending a cancer centre, affecting 41.2% of the patients. Although majority of patients who suffered from pain reported this to doctors, much more medical effort is needed to help patients to relieve their pain and proper complementary therapy could be considered.
... It also reduced thermal and mechanical hypoalgesia, that is, sensory loss, which is a major cause of foot ulceration and amputation in human subjects with diabetes mellitus [1]. Several herbal extracts and other products have been reported to alleviate diabetic neuropathic pain and sensory loss in diabetic rats and mice [40,41]. However, to our knowledge, only primrose oil reversed MNCV and SNCV deficits as effectively [42] as it was observed in our study with PMI-5011. ...
Article
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Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S)-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mg kg(-1) d(-1), 7 weeks) normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease.
... Thus, pursuing improved treatments for neuropathic pain is one of the utmost social and clinical needs. With an increasing number of herbals/phytochemicals being developed for psychiatric medicine (Chiappedi and Bejor, 2010), including analgesics (Kanodia et al., 2010;Zareba, 2009), the use of complementary and alternative therapies may provide a new way to treat refractory neuropathic pain. ...
Article
Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45 mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6-hydroxydopamine (6-OHDA), or depletion of descending serotonin by p-chlorophenylalanine (PCPA), abolished curcumin's antinociceptive effect on mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic action of curcumin on mechanical stimuli was totally blocked by chronic co-treatment with the β(2)-adrenoceptor antagonist ICI 118,551, or by acute co-treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co-treatment with the 5-HT(1A) receptor antagonist WAY-100635 chronically, or with the irreversible mu-opioid receptor antangonist β-funaltrexamine acutely, completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli. Collectively, these findings indicate that the descending monoamine system (coupled with spinal β(2)-adrenoceptor and 5-HT(1A) receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
... Added to this lure is the prospect of new drug discovery; amongst numerous examples of drugs originating from plants that have central nervous system (CNS) effects are ephedrine (Ephedra sinica Stapf), hyoscine (Hyoscyamus niger L.), morphine (Papaver somniferum L.), physostigmine (Physostigma venenosum Balf.), and galantamine from species of Galanthus and Narcissus. Precedents for the continuing discovery of plants or phytochemicals in other areas of medicine include numerous oncology medicines [7,8], potential drugs for infectious diseases (e.g., antibacterials and antivirals) [7], for analgesia [9], and for immunological and inflammatory diseases [7]. ...
Article
An escalating "epidemic" of diseases like Alzheimer's has not yet been met by effective symptomatic treatments or preventative strategies. Among a few current prescription drugs are cholinesterase inhibitors including galantamine, originating from the snowdrop. Research into ethnobotanicals for memory or cognition has burgeoned in recent years. Based on a multi-faceted review of medicinal plants or phytochemicals, including traditional uses, relevant bioactivities, psychological and clinical evidence on efficacy and safety, this overview focuses on those for which there is promising clinical trial evidence in people with dementia, together with at least one other of these lines of supporting evidence. With respect to cognitive function, such plants reviewed include sage, Ginkgo biloba, and complex mixtures of other traditional remedies. Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population). The ultimate goal of disease prevention is considered from the perspective of limited epidemiological and clinical trial evidence to date. The potential value of numerous plant extracts or chemicals (e.g., curcumin) with neuroprotective but as yet no clinical data are reviewed. Given intense clinical need and carer concerns, which lead to exploration of such alternatives as herbal medicines, the following research priorities are indicated: investigating botanical agents which enhance cognition in populations with mild memory impairment or at earliest disease stages, and those for BPSD in people with dementia at more advanced stages; establishing an ongoing authoritative database on herbal medicine for dementia; and further epidemiological and follow up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention.
... Many believe that medicinal plants, due to their lack of or negligible side effects and relative low cost, are preferable to conventional medicines. The present results regarding the positive correlation between administration of botanicals and naturaceuticals, prophylaxis and treatment of heart diseases, and diminishing their casual agents are in accordance with previous observations [1][2][3][4][5][6]10,[23][24][25][26][27][28]. Increase of exercise stability along with decrease of heart rate and blood pressure during maximum activity was observed after administration of garlic and hawthorn [5,6,23]. ...
Article
Introduction; Medicinal plants possessing significant beneficial properties are an ideal choice as complementary medicinal strategies. Positive effects of medicinal plants on the cardiovascular system have been consistently reported. Here, we report the improvement of exercise tolerance of patients suffering from stable chest angina as a result of reduction in serum lipids by administration of Stragol™ oral drop, a consortium of seven medicinal plant extracts. Methodology; Forty patients suffering from stable chest angina were treated with or without Stragol™ herbal heart drop for four weeks besides taking conventional medicines. The study assessed the effects of Stragol™ on critical influential factors in cardiovascular functions, i.e., serum lipids, blood sugar and exercise tolerance. Biochemical examination of blood for serum lipids and blood sugar was performed before and after treatment in both experimental and control groups. Results; Analysis of data revealed a considerable reduction in serum LDL cholesterol, total cholesterol and triglyceride in experimental group. In addition, a significant improvement in exercise tolerance of the patients was observed after treatment with Stragol™, most likely by reducing the level of blood lipids and resultant reduction of atherosclerosis. Conclusion; Four weeks administration of seven medicinal plant extracts with high levels of glycosides and flavonoids in the form of Stragol™ oral drop is an effective complementary strategy to significantly lower the risk of atherosclerosis and downstream heart problems.
... Throughout history, natural products and plant food supplements have contributed unequivocally to the pain and inflammation control (Di Lorenzo et al., 2013), the example of morphine isolated from Papaver somniferum and more recently, ziconotide, a peptide from snails which is used for the treatment of chronic pain. Hence, herbal medicines used in pain therapy can contribute to restoring the quality of life to a patient and may enhance conventional management of different types of pain, such as rheumatologic diseases, back pain, cancer, diabetic peripheral neuropathy and migraine (Zareba, 2009). ...
... (Ginkgoaceae) are shown to have potential in different types of experimentally induced neuropathic pain (Kim et al., 2009;Muthuraman et al., 2008;Wirth et al., 2005). Some clinical reports have also advocated beneficial effect of drugs from plant origin in neuropathic pain conditions (Ellis et al., 2009;Zareba, 2009). ...
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Context: Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity. Objective: The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model. Materials and methods: Vincristine sulfate (0.1 mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14 d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10 mg/kg, p.o.) and curcumin (15, 30, and 60 mg/kg, p.o.) were administered for 14 consecutive days. Results: Curcumin at 60 mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p < 0.001) and allodynia (p < 0.001); mechanical hyperalgesia (p < 0.001); functional loss (p < 0.001); and in the delayed phase of formalin test (p < 0.001). Curcumin at 30 and 60 mg/kg exhibited significant changes (p < 0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice. Conclusion: Curcumin at 30 and 60 mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.
... [19,26,41]. Some clinical reports have also advocated beneficial effect of drugs from plant origin in neuropathic pain conditions [10,43]. ...
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Hyperalgesia, allodynia, delayed motor nerve conduction velocity, oxidative stress and axonal damage are signs and symptoms of chemotherapy induced peripheral neuropathy (CIPN). Present treatment/preventive strategies of CIPN are futile and the neuropathy may even lead to discontinuation of chemotherapy. In this study, we evaluated the protective effect of tetrahydrocurcumin (THC) 40 and 80mg/kg in experimental vincristine induced neuropathy in rats. Hyperalgesia was assessed by hot plate (thermal), Randall-Selitto (mechanical) test, allodynia was assessed by cold plate (thermal) test, functional loss was measured by sciatic function index, nociception was evaluated by formalin test. Neurophysiological recordings were carried out to assess motor nerve conduction velocity. Total calcium levels, oxidative stress and TNF-α was measured in sciatic nerve tissue homogenate to assess neuropathy. Histopathological changes was observed on sciatic nerve to assess the protective effect of THC against the vincristine. Pregabalin was used as a standard in this study. Rats administered with THC at 80mg/kg significantly attenuated the vincristine induced neuropathic pain manifestations which may be due to its multiple actions including anti-nociceptive, anti-inflammatory, neuroprotective, calcium inhibitory and antioxidant effect. This study delineates that THC can be a promising candidate for the prevention of CIPN by chemotherapeutic agents. Copyright © 2015. Published by Elsevier Ireland Ltd.
... In the course of time a different approach has been adopted in the search of compounds from medicinal plants, due to the high cost of compound synthesis and also because more people started looking for more natural forms of medication. Complementary and alternative medicines (CAM) became popular, using herbal therapy that has its focus on using the entire extract rather than a single compound (Desmarchelier, 2008;Zareba, 2009). According to WHO the commercialisation of these products has generated income of US$ 5 billion in 2003-2004 for western societies and for China US$ 14 billion in 2005. ...
Article
The chemical profile and medicinal effects of H. crenata on two mouse models were evaluated in order to quantify pharmacological effects caused by bioactive compounds. A survey was conducted regarding traditional preparation and use of H. crenata in Brazil (20 regular users). The extraction methods reported were: (i) decoction (boiling in water); (ii) infusion (tea); (iii) cold extraction (water); (iv) cold extraction (15% alcohol); and (v) cold extraction (40% alcohol). The decoction extract (i) showed the highest concentration of dry matter (4.55 g/L). The traditional uses most frequently reported were for forms of mild pain (11/20 - headache, stomach discomfort, menstrual pain) or treatment of flu/fever (6/20). Based on this traditional use, a study was conducted on the antinociceptive effects of the decoction extract (i) in 8 C57/BL6 mice per treatment. Orally administered doses of 15 and 150 mg/kg b.w. were compared with water and Indomethacin 10 mg/kg b.w in models of phasic pain (Hargreaves test) and tonic pain (acetic acid-induced writhing). In both models the treatment effects were significantly different from the water control treatment, but not from the positive control Indomethacin. HPLC analysis of the decoction extract compared with an authentic standard of salicylic acid showed that salicylic acid was not detectable in the extract.
... 1 Current analgesics continue to attract notice due to safety concerns and the potential risks that have sprung up recently despite their widespread use. 2 Even though a multitude of pharmaceutical products such as nonsteroidal anti-inflammatory drugs, opioids, tricyclic antidepressants and anticonvulsants on the market for pain treatment, many patients turn to herbal remedies because of the side effects and tolerability problems of existing drugs. 3 Herbal remedies are in great demand in pain treatment due to their efficacy and safety. 4 Even though synthetic drugs have a significant share in the pharmaceutical industry, drugs made from natural active substances and compounds make up almost 50 % of the drugs currently used. ...
... Natural products are considered important sources of investigation of potential new drugs, and studies of bioactive molecules effective in the treatment of acute and chronic pain conditions are promising [9][10][11]. Annona crassiflora Mart., popularly known as araticum, is a native species of the Brazilian Savanna biome belonging to the Annonaceae family and represents a potential source for painful treatment [12]. ...
Article
Pain relief represents a critical unresolved medical need. Consequently, the search for new analgesic agents is intensively studied. Annona crassiflora, a native species of the Brazilian Savanna, represents a potential source for painful treatment. This study aimed to investigate the antinociceptive potential of A. crassiflora fruit peel, focusing on its major alkaloid, stephalagine, in animal models of pain evoked by the activation of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels. Male C57BL/6/J mice were submitted to formalin-, cinnamaldehyde-, and capsaicin-induced nociception tests to assess nociceptive behavior, and to the open-field and rotarod tests for motor performance analyses. Moreover, the stephalagine's effect was tested on capsaicin- and cinnamaldehyde-induced Ca2+ influx in spinal cord synaptosomes. In silico assessments of the absorption, distribution, metabolism and central nervous system permeability of stephalagine were carried out. The ethanol extract and alkaloidal fraction reduced the nociception induced by formalin. When administered by oral route (1 mg/kg), stephalagine reduced the spontaneous nociception and paw edema induced by TRPV1 agonist, capsaicin, and by TRPA1 agonists, cinnamaldehyde- and formalin, without altering the animals' locomotor activity. The prediction of in silico pharmacokinetic properties of stephalagine suggests its capacity to cross the blood-brain barrier. Furthermore, this alkaloid reduces the capsaicin- and cinnamaldehyde-mediated Ca2+ influx, indicating a possible modulation of TRPV1 and TRPA1 channels, respectively. Together, our results support the antinociceptive and anti-edematogenic effects of the A. crassiflora fruit peel and suggest that these effects are triggered, at least in part, by TRPV1 and TRPA1 modulation by stephalagine.
... Pain is a common noxious phenomenon, causing one of the most common healthcare problems and leads to different complicated physical and psychological problems [1] . Pain management with several pain controlling drugs cause only symptomatic relief. ...
Article
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The widely used analgesic drugs are associated with several harmful effects, which initiate search for new drug development from medicinal plants with better therapeutic efficacy and minimum toxicity. Rhizophora mucronata is a very popular mangrove plant which has been used as ethno-medicine from ancient time. In the present study the ethanolic extract of Rhizophora mucronata L. leaves was found to be safe upto 2gm/kg body weight (orally) in mice in acute toxicity study. The extract in 200 mg/kg body weight dose (orally) showed significant inhibition in acetic acid induced writhing response in mice. In the hot plate method, it increased the latency period than control to some extent, but in tail immersion test, did not showed any significant result. Present study revealed that the ethanolic extract of Rhizophora mucronata L. (Sunderban mangrove) leaves is rich in tannin, flavonoids, polyphenols and possess potential peripheral analgesic and mild central analgesic action.
... To date, little is known about the pathophysiology of VIPN and no effective cure is available. Instead, management is limited to pain relief with anti-epileptics, anti-depressants and opioids, which can induce a myriad of side effects (Zareba, 2009). Therefore, a high medical need for an effective treatment for chemotherapy-induced peripheral neuropathies still exists (Cavaletti and Marmiroli, 2010;Majithia et al., 2016). ...
Article
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As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy. The aim of this study was to investigate the potential of specific histone deacetylase 6 (HDAC6) inhibitors as a preventive therapy for CIPN using multiple rodent models for vincristine-induced peripheral neuropathies (VIPN). HDAC6 inhibition increased the level of acetylated α-tubulin in tissues of rodents undergoing vincristine-based chemotherapy, which correlates to a reduced severity of the neurological symptoms, both at the electrophysiological and the behavioral level. Mechanistically, disturbances in axonal transport of mitochondria is considered as an important contributing factor in the pathophysiology of VIPN. As vincristine interferes with the polymerization of microtubules, we investigated whether disturbances in axonal transport could contribute to VIPN. We observed that increasing α-tubulin acetylation through HDAC6 inhibition restores vincristine-induced defects of axonal transport in cultured dorsal root ganglion neurons. Finally, we assured that HDAC6-inhibition offers neuroprotection without interfering with the anti-cancer efficacy of vincristine using a mouse model for acute lymphoblastic leukemia. Taken together, our results emphasize the therapeutic potential of HDAC6 inhibitors with beneficial effects both on vincristine-induced neurotoxicity, as well as on tumor proliferation.
... However, there is a need to discover new agents due to drug interactions, side effects and tolerability problems encountered with existing drugs. Thus, the interest in treatment with herbal medicines, which have fewer side effects and stronger therapeutic results, has considerably increased [2][3][4]. Protocatechuic acid (3,4-dihydroxybenzoic acid) is a phenolic compound that has been recently drawing attention for its biologic effects [5,6]. Protocatechuic acid can easily crosses the blood brain barrier. ...
Article
Background: Protocatechuic acid is an antioxidant which is shown to have analgesic activity in limited studies. However, the mechanisms of action remain unclear. Objectives: It is aimed to investigate the possible contribution of cannabinoid system that supresses the nociceptive process by the activation of CB1 and CB2 receptors in central and peripheral levels of pain pathways, to the analgesic activity of protocatechuic acid. Methods: The analgesic activity of protocatechuic acid was determined at the doses of 75, 150 and 300 mg/kg (i.p.) by acetic acid-induced writhing and tail-immersion tests in mice. The results were compared to the analgesic effect of 300 mg/kg (i.p.) dipyrone and non-specific CB receptor agonist 5 mg/kg (i.p.) WIN 55,212-2. For investigating the contribution of cannabinoid system to protocatechuic acid analgesia; pre-treatment with 8 mg/kg (i.p.) CB1 antagonist AM251 and 8 mg/kg (i.p.) CB2 antagonist AM630 were performed separately before 300 mg/kg protocatechuic acid administration. Results: It was determined that protocatechuic acid has dose-dependent analgesic effect independently from locomotor activity and is comparable with effects of dipyrone and WIN 55,212-2. Pre-treatment with CB1 receptor antagonist AM251 significantly antagonized the protocatechuic acid-induced analgesia in the tail-immersion and writhing tests, whereas pre-treatment of CB2 receptor antagonist AM630 was found to be effective only in the tail-immersion test. Conclusion: It is concluded that cannabinoid modulation contributes to the analgesic effect of protocatechuic acid in spinal level rather than peripheral. CB1 receptor stimulation rather than CB2 receptor stimulation mediates the analgesic effect of protocatechuic acid in both levels, especially peripheral. Graphical abstract Protocatechuic acid inhibits pain response via cannabinoidergic system.
... Therefore, agents that act on inflammation could be potential targets for neuropathic pain therapy. However, conventional analgesic therapeutics for neuropathic pain, such as tricyclic antidepressants, opioids analgesics, and non-steroidal anti-inflammatory drugs (NSAIDs), have remained unsatisfactory due to their various adverse effects, withdrawal syndromes, extensive limitations, and multiple pathological mechanisms [21,22]. Thus, it is imperative to explore novel therapeutic agents that provide additional options for safe and effective neuropathic pain remedies. ...
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Neuropathic pain is an intractable disease with few definitive therapeutic options. Anethole (AN) has been confirmed to possess potent anti-inflammatory and neuroprotective properties, but its effect on neuropathic pain has not been reported. The present study was designed to investigate the antinociceptive effect of AN on chronic constriction injury (CCI)-induced neuropathic pain in mice. AN (125, 250, and 500 mg/kg) and pregabalin (40 mg/kg) were intragastric administered for 8 consecutive days from the 7th day post-surgery. Behavioral parameters were measured on different days, namely, 0, 7, 8, 10, 12, and 14, from CCI operation. Additionally, electrophysiological and histopathological changes were analyzed on the 14th day. Afterward, immunofluorescence and Western blot were utilized to examine the activation of glial cells and the expression of inflammatory cytokines, respectively. AN treatment of CCI mice considerably alleviated hyperalgesia and allodynia, ameliorated abnormal sciatic nerve conduction, and restored injured sciatic nerves in a dose-dependent manner. Furthermore, AN suppressed the activation of glial cells, down-regulated pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1β), and up-regulated the anti-inflammatory cytokine (IL-10). These assays first indicated that AN exerted an antinociceptive effect on CCI-induced neuropathic pain, and might be attributed to the anti-inflammatory and neuroprotective activities of AN.
... In traditional medicine, aqueous decoctions of Paeonia have been used against several types of seizures. Important crude drugs extracted from Paeonias species in Chinese, Korean, Japanese, and Vietnamese traditional medicine, used as an anticoagulant, anti-inflammatory, analgesic, and sedative agent (Braca et al., 2008;Zareba, 2009;Koyunoğlu et al., 2012). There are many medications available for disease joint pain, swelling and inflammation like nonsteroidal anti-inflammatory drugs (NSAIDs-such as aspirin, ibuprofen or naproxen). ...
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Resumen Context: Paeonia mascula is used in traditional medicine in North of Algeria for its anti-inflammatory activity. Aims: To evaluate the analgesic and the anti-inflammatory effects of the ethanolic extract of Paeonia mascula (EPM) in mice. Methods: The analgesic activity of EPM was evaluated on the chemical nociception in the animal models of acetic acid-induced writhing and formalin-induced hind paw licking/biting, whereas xylene-induced ear edema and multiapplication of TPA (12-O-tetradecanoylphorbol-13-acetate) were used to determine anti-inflammatory effects of EPM. Results: EPM (100 and 250 mg/kg) produced a significant dose-dependent inhibition of pain-related behaviors elicited by acetic acid. Also, EPM reduced both early and late phases of the formalin test. However, its inhibitory effect was more significant on tonic inflammatory phase, may be related to the anti-inflammatory abilities of this extract. Also, EPM decreased ear edema in acute and sub-chronic models used in the present study. Conclusions: These findings suggest the ethanolic extract from aerial parts of Paeonia mascula presents significant anti-inflammatory and anti-nociceptive effects on chemical behavioral models of nociception and inflammation in mice. Contexto: Paeonia mascula se utiliza en la medicina tradicional en el norte de Argelia por su actividad anti-inflamatoria. Objetivos: Evaluar la actividad analgésica y antiinflamatoria del extracto etanólico de Paeonia mascula (EPM) en ratones. Métodos: El perfil analgésico se evaluó mediante la prueba de constricciones abdominales inducidas por ácido acético y la prueba de formalina 1%. Con la finalidad de estudiar su efecto antiinflamatorio se implementaron dos modelos de edema auricular en condiciones agudas (edema inducido por xileno) y en condiciones sub-crónicas [edema inducido por aplicaciones múltiples de TPA (12-O-tetradecanoilforbol-13-acetato)]. Resultados: El extracto etanólico de Paeonia mascula inhibió de forma dependiente de la dosis las conductas relacionadas con el dolor inducidas por ácido acético. Además, EPM redujo ambas fases, la temprana y la tardía en la prueba de la formalina. Sin embargo, su efecto inhibitorio fue más significativo sobre la fase tónica inflamatoria. Este efecto pudiera estar relacionado con la actividad antiinflamatoria del extracto. También EPM redujo significativamente el edema auricular en los modelos (agudo y sub-crónico) utilizados en el estudio. Conclusiones: Estos hallazgos sugieren que el extracto etanólico de partes aéreas de Paeonia mascula presenta efectos antiinflamatorios y antinociceptivos en modelos agudos de nocicepción química e inflamación en ratones.
... In traditional medicine, aqueous decoctions of Paeonia have been used against several types of seizures. Important crude drugs extracted from Paeonias species in Chinese, Korean, Japanese, and Vietnamese traditional medicine, used as an anticoagulant, anti-inflammatory, analgesic, and sedative agent (Braca et al., 2008;Zareba, 2009;Koyunoğlu et al., 2012). There are many medications available for disease joint pain, swelling and inflammation like nonsteroidal anti-inflammatory drugs (NSAIDs-such as aspirin, ibuprofen or naproxen). ...
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Context: Paeonia mascula is used in traditional medicine in North of Algeria for its anti-inflammatory activity. Aims: To evaluate the analgesic and the anti-inflammatory effects of the ethanolic extract of Paeonia mascula (EPM) in mice. Methods: The analgesic activity of EPM was evaluated on the chemical nociception in the animal models of acetic acid-induced writhing and formalin-induced hind paw licking/biting, whereas xylene-induced ear edema and multiapplication of TPA (12-O-tetradecanoylphorbol-13-acetate) were used to determine anti-inflammatory effects of EPM. Results: EPM (100 and 250 mg/kg) produced a significant dose-dependent inhibition of pain-related behaviors elicited by acetic acid. Also, EPM reduced both early and late phases of the formalin test. However, its inhibitory effect was more significant on tonic inflammatory phase, may be related to the anti-inflammatory abilities of this extract. Also, EPM decreased ear edema in acute and sub-chronic models used in the present study. Conclusions: These findings suggest the ethanolic extract from aerial parts of Paeonia mascula presents significant anti-inflammatory and anti-nociceptive effects on chemical behavioral models of nociception and inflammation in mice. Keywords: analgesic; formalin; inflammation; pain.
... For reference, of the 1,500+ research abstracts examined in this systemic review, no other psychotropic phytochemical reached the level of more than 1 abstract and none were included for full-text review. Whether any of the phytochemicals examined in this systematic review will ultimately prove valuable for the management of pain in cancer therapy remains to be determined [40]. However, the additional sociological and political barriers to scientific investigation must be considered in the case of psychotropic phytochemicals, such as marijuana. ...
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Pain in cancer therapy is a common condition and there is a need for new options in therapeutic management. While phytochemicals have been proposed as one pain management solution, knowledge of their utility is limited. The objective of this study was to perform a systematic review of the biomedical literature for the use of phytochemicals for management of cancer therapy pain in human subjects. Of an initial database search of 1,603 abstracts, 32 full-text articles were eligible for further assessment. Only 7 of these articles met all inclusion criteria for this systematic review. The average relative risk of phytochemical versus control was 1.03 [95% CI 0.59 to 2.06]. In other words (although not statistically significant), patients treated with phytochemicals were slightly more likely than patients treated with control to obtain successful management of pain in cancer therapy. We identified a lack of quality research literature on this subject and thus were unable to demonstrate a clear therapeutic benefit for either general or specific use of phytochemicals in the management of cancer pain. This lack of data is especially apparent for psychotropic phytochemicals, such as the Cannabis plant (marijuana). Additional implications of our findings are also explored.
... Phytomedicine is considered a useful approach to treat refractory neuropathic pain [3,4]. In regard to this, some natural products that produce antiallodynic and anti-hyperalgesic effects in neuropathic pain, like flavonoids, have been currently reported [5][6][7]. ...
Article
Flavonoids are natural compounds showing anti-hyperalgesic activity in models of pain. Diosmin is a compound poorly studied in the treatment of neuropathic pain. This study evaluates the anti-hyperalgesic actions of diosmin and possible mechanisms of action involved by using a neuropathic pain model in rats. Experimental neuropathic pain was induced by chronic constriction injury (CCI) in male Wistar rats, then aesthesiometric index and plantar tests were assessed to evaluate mechanical and thermal hyperalgesia, respectively, in order to explore the analgesic effects of acute and sub-chronic treatment with diosmin. The GABAA, 5-HT1A, D2-like and opioid receptors participation, as well as levels of TNF-α, IL-1β and IL-6, were evaluated in the spinal cord and sciatic nerve tissues after acute and subchronic diosmin administration. In addition, the presence of diosmin on cerebral samples was determined by UHPLC-MS analysis. Acute and sub-chronic treatment with diosmin significantly diminished the mechanical and thermal hyperalgesia induced by CCI in rats. This anti-hyperalgesic effects of diosmin were modified in the presence of naloxone (1mg/kg, i.p.) and haloperidol (0.1mg/kg, i.p.), but not by GABAA and 5-HT1A receptor antagonists. The anti-hyperalgesic effects of diosmin were also linked with reduced levels of TNF-α, IL-1β and IL-6. The presence of diosmin in the cerebral samples was confirmed by chromatographic analysis. In conclusion, our results provide evidence that diosmin produces significant anti-hyperalgesic effects acting at central level by an opioid and D2 dopaminergic receptors participation, and at peripheral level by reducing proinflammatory cytokines.
... Despite the huge amount of pain relievers available to treat a number of pain-related diseases, their large range of side effects and low efficacy lead patients to switch to alternative medicines, such as herbal medicines (Quintans et al., 2014;Zareba, 2009). ...
Article
Ethnopharmacological relevance: The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. Aim of the study: The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. Material and methods: The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect. Results: EOHs presented antinociceptive effect at 300 and 1000mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED50 =292mg/kg), and 85% and 100% during de second phase (ED50 =205mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000mg/kg, ED50 =660mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000mg/kg, respectively; ED50 402mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000mg/kg, respectively; with ED50 =198mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300mg/kg) does not show antinociceptive effect. Conclusions: This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs activity, which was remarkably potent and efficient in inhibiting pain evoked by menthol, a TRPM8 channel activator. TRPM8 channels from TRPV1+ C-fibers, but not TRPM8+ C-fibers nor TRPM8+ Aδ mechanosensory fibers, mediate EOHs analgesic effects.
... Therefore, treatment of neuropathic syndromes remains a challenge on account of their complex natural history, unclear etiology and poor response to drugs [10]. Some clinical reports have advocated beneficial effect of drugs from plant origin in neuropathic pain conditions [11]. ...
Article
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Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T-AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-α, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti-inflammatory actions.
Article
Inflammatory pain and neuropathic pain are major health issues that represent considerable social and economic burden world wide. In this study we investigated the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. Chronic constriction injury (CCI), L5 spinal nerve ligation (L5 SNL), diabetes, and chemotherapeutics inducing allodynia were used to test whether repeated treatment with obtusifolin and gluco-obtusifolin ameliorated neuropathic pain. Finally, we explored whether obtusifolin and gluco-obtusifolin altered the degree of neuroinflammation in rat spinal cord after CFA administration and CCI induction. Obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced licking/biting time in dose-dependent manner in phase 2of formalin-induced behavior in mice. Furthermore, repeated administration of obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats. Levels of activated NF-κB and proinflammatory cytokines (IL-1β, IL-6, TNF-α) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and obtusifolin and gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain, and that this activity is associated with modulation of neuroinflammation in spinal cord.
Article
Complementary or alternative medicine pain management techniques, used alone or integrated into Western medicine-based protocols, include, but are not limited to acupuncture, herbal medicine, homeopathic remedies, chiropractic, and massage. The mechanisms underlying traditional Chinese medicine (TCM) methods, such as acupuncture and herbal medicine, can be approached from many angles. The TCM and homeopathy offer veterinarians complementary or alternative options for managing pain in their patients. These tools may allow for better clinical control with fewer adverse effects than Western pharmaceuticals. As the use of these complementary methods grows among human patients, it is likely that there will be a greater demand for such therapies in veterinary patients.
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Introduction: Pain is a common symptom in cancer patients, but very little information about the prevalence, severity, and treatment of pain in cancer patients in Singapore is available. Therefore, our prospective survey in the National Cancer Centre (NCC) outpatients is incorporated in this report. In addition, a review concerning the recent advances on non-interventional pain management in cancer treatment, which is relevant in the context, is discussed. Materials and methods: For the prospective survey, a questionnaire was distributed for self-administration by patients while waiting for consultation at the NCC outpatient departments. Literature searches on advances in pain management were conducted, reviewed and discussed. Results: In the last decade, there have been advances in pain pharmacology ranging from wider therapeutic options and management approaches to novel delivery techniques. Acupuncture and massage therapy became increasingly popular among cancer patients. Some clinical trials of acupuncture show benefits in palliation of cancer pain. From the prospective survey, 41.2% of the responders reported pain in the past week, and only 70.8% talked to their doctors about their pain. One third of the patients received analgesics. Of these, 86.5% said that they were taking the prescribed medications, however, 37.4% admitted to having difficulties taking them. Non-drug methods were used by 25.4% of the patients. Medicated oil, cream or gel was used by 49.3%; only 2.6% reported use of Chinese herbs. Conclusion: Pain is a significant symptom in outpatients attending a cancer centre, affecting 41.2% of the patients. Although majority of patients who suffered from pain reported this to doctors, much more medical effort is needed to help patients to relieve their pain and proper complementary therapy could be considered.
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Crude alkaloidal extraction from Gelsemium elegans Benth. produces analgesic property. However, its clinical utility has been obstructed by its narrow therapeutic index. Here, we investigated the potential of koumine, a monomer of Gelsemium alkaloids, to reduce both inflammatory and neuropathic pain. Interestingly, allopregnanolone, a neurosteroid, appeared to mediate the reduction of neuropathic pain. The potential anti-inflammatory pain effects of koumine were evaluated by acetic acid-, formalin- and complete Freund's adjuvant (CFA) -induced nociceptive behaviors in mice. Chronic constriction injury (CCI) and L5 spinal nerve ligation (L5 SNL), inducing thermal hyperalgesia and mechanical allodynia in rats, were used to test whether repeated treatment of koumine ameliorated neuropathic pain. Finally, we explored if koumine altered the level of neurosteroids in rat spinal cord of CCI neuropathy using liquid chromatography-tandem mass spectrometry. Koumine dose-dependently reduced the acetic acid-induced writhes and formalin-induced licking/biting time of Phase II in mice. Repeated administrations of koumine also dose-dependently reversed the CFA-, CCI- and L5 SNL-induced thermal hyperalgesia, as well as, CCI- and L5 SNL-induced mechanical allodynia in rats. The level of allopregnanolone, but not pregnenolone, in the L5-6 spinal cord was elevated by repeated treatment of koumine in CCI-induced neuropathic rats. These results demonstrate that koumine has a significant analgesic effect in rodent behavioral models of inflammatory and neuropathic pain, and that the reduction in neuropathic pain may be associated with the upregulation of allopregnanolone in the spinal cord.
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A polysaccharide (SFWP), with a molecular weight of 51 kDa, was successfully purified from the roots of Sophora flavescens and the antinociceptive actions of SFWP were evaluated using acetic acid induced writhing, tail flick, and formalin tests in mice. GC–MS results showed that SFWP had a backbone composed of (1 → 2)-linked Glc, (1 → 2,6)-inked Gal and (1 → 3,6)-inked Man residues, which were terminated with (1 → )-inked Xyl and (1 → )-inked Ara at O-6 of (1 → 2,6)-inked Gal and (1 → 3,6)-inked Man along the main chain, in the ratio of 2.0: 1.02: 1.09: 1.10: 0.98. Data showed that SFWP (100, 200 and 400 mg/kg) significantly reduced the number of writhings induced by acetic acid in a dose-dependent manner. However, SFWP did not produce analgesia in tail-flick test. Moreover SFWP strongly attenuated the formalin-induced flinching behaviour in the second phases but not in the first phase in a dose-dependent manner. These results revealed that SFWP could be used safely to attenuate both inflammatory and peripheral neuropathic pain.
Article
The prevalence of spinal symptoms in Western industrialised countries ranges up to 80 %. Back pain ranks second among the most common reasons to seek medical advice. The resulting financial burden on the health-care system is proportional to the subjectively experienced pain. The aim of the present study was to determine whether the use of magnetic resonance therapy alters the duration of sickness absence in patients with discogenic radiculopathy. In a double-blind prospective randomised study, the use of magnetic resonance therapy for back pain in patients with discogenic radiculopathy was evaluated in the context of health economics. Patients aged 20 to 55 years with lumboischialgia and no indication for surgery were included in the study. The primary variable was the number of days of sickness absence in a study group before and after magnetic field therapy, and in a control group. The number of days of sickness absence was determined on the basis of a pain diary and by telephone inquiry. Patients who were treated with an activated magnetic resonance therapy device had significantly fewer days of sickness absence (p = 0.009) when evaluated by personal telephone calls. The duration of sickness absence before therapy was 14.7 days and that after therapy 5.8 days. In contrast, the days of sickness absence in the control group were 7.6 days before therapy and 13.8 days after therapy. The duration of symptoms was negatively correlated with the days of sickness absence. Patients who reported a burden at work had more days of sickness absence (8.3 days) than those with no burden at work (3.2 days). This correlation does not apply to familial burden. The cost-effectiveness analysis showed different degrees of compensation of the cost of magnetic resonance therapy, depending on the occupational group. Direct and indirect costs of magnetic resonance therapy were compensated by 16.9 fewer days of sickness absence among workers, 11.4 fewer days of sickness absence among employees, and 9.1 fewer days of sickness absence among civil servants. Based on the number of days of sickness absence, the study confirmed that a relatively economical alternative technique is able to provide pain relief as well as benefit the health economy. Unemployed patients or patients who have submitted an application for a pension may be problematic because they may not wish to be pronounced healthy by their doctors.
Article
The study investigates the protective effect of Acorus calamus L. (AC) in vincristine-induced painful neuropathy. Vincristine (75μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy in rats. Various tests were performed to assess the degree of painful neuropathy at different days i.e., 0, 1, 7, 14, and 21st day. Sciatic nerve TNF-α, superoxide anion generation, total calcium, and myeloperoxidase activity level were also estimated after 21st day of study. Hydro-alcoholic extract of AC (HAE-AC, 100 and 200mg/kg, p.o.) and pregabalin (10mg/kg, p.o.) were administered for 14 consecutive days. Vincristine significantly induced neuropathic pain manifested in the terms of thermal hyperalgesia and allodynia (increase in hind paw licking, lifting or jumping from hot plate); mechanical hyperalgesia (increase in left hind paw lifting duration in pin-prick test) and allodynia (left hind paw withdrawal reflexes to non-noxious stimuli in Von Frey test); and sciatic functional index (analysis of footprints of the feet) along with rise in the levels of various biochemicals. HAE-AC attenuated vincristine induced behavioral, and biochemical changes comparable to that of pregabalin (positive control). HAE-AC attenuated vincristine induced painful neuropathy, which may be attributed to its multiple effects including anti-oxidative, anti-inflammatory, and calcium inhibitory actions.
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This study aims to investigate and announce orally transmitted traditional plant-based therapies for pain relief in North Jeolla Province, Korea. Data was collected with semi-structured questionnaires through the participatory rural appraisal method. This study reveals that overall 23 pain ailments have been treated with a total of 82 species of medicinal plants belonging to 74 genera in 45 families. This study also reports 313 different modes of plant-based therapeutic application of medicinal material. The informant consensus factor for pleurodynia, slipped disk and frozen shoulder is 1.00, the highest among 23 different pain ailments, followed by lumbago, chronic myofascial pain, melosalgia, sinews and joints pain, arthralgia, carpal tunnel syndrome, etc. Medicinal plants with 100% fidelity level and above three mentions among informants were 15 species. This study can help to preserve the traditional knowledge and local health traditions of North Jeolla Province amidst rapid industrialization and urbanization. The findings of this study warrant follow-up clinical research to determine the most effective traditional remedies towards development of herbal medicinal products for integration into the Korean healthcare system. These results will help to prepare the way for advanced research such as new medicines and new therapies that could be of help clinically.
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Neuropathic pain is a major health issue that represents considerable social and economic burden worldwidely. In this study, we investigated the potential of catalpol, an iridoid glucoside of Rehmannia glutinosa Steud, to alleviate neuropathic pain. The potential analgesic effects of catalpol were evaluated by chronic constriction injury (CCI) and lumbar 5 spinal nerve ligation (L5 SNL) model. In addition, we explored whether catalpol altered the degree of microglia activation and neuroinflammation in rat spinal cord after CCI induction. Repeated administration of catalpol (1, 5, 25, and 125 mg/kg) reversed mechanical allodynia induced by CCI and L5 SNL in a dose-dependent manner in rats. Levels of activated microglia, activated NF-κB, and proinflammatory cytokines (IL-1β, IL-6, TNF-α) in lumber spinal cord were elevated in rats following CCI induction, and catalpol significantly inhibited these effects. Our results demonstrated that catalpol produces significant antinociceptive action in rodent behavioral models of neuropathic pain and that this effect is associated with modulation of neuroinflammation in spinal cord.
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Objective: To assess the clinical efficacy and adverse effects of gamma-linolenic acid (GLA), a plant seed oil-derived unsaturated fatty acid that suppresses inflammation and joint tissue injury in animal models, in the treatment of active rheumatoid arthritis (RA). Methods: Fifty-six patients with active RA were randomized to treatment groups in a 6-month, double-blind trial of GLA versus placebo. This was followed by a 6-month, single-blind trial during which all patients received GLA. Patients were treated with 2.8 gm/day of GLA as the free fatty acid or with sunflower seed oil (placebo) administered in identical capsules. Results: Treatment with GLA for 6 months resulted in statistically significant and clinically relevant reductions in the signs and symptoms of disease activity in patients with RA. Overall meaningful responses (at least 25% improvement in 4 measures) were also better in the GLA treatment group (14 of 22 patients versus 4 of 19 in the placebo group; P = 0.015). During the second 6 months, both groups exhibited improvement in disease activity. Thus, patients taking GLA during the entire study showed progressive improvement during the second 6 months. In this group, 16 of 21 patients showed meaningful improvement at 12 months compared with study entry. Conclusion: GLA at doses used in this study is a well-tolerated and effective treatment for active RA. GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial. It is not approved in the United States for the treatment of any condition, and should not be viewed as therapy for any disease. Further controlled studies of its in RA are warranted.
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In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents.
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It is widely recognized that alternative therapies have increased in use, and pharmacists are being asked more often to provide information on these products. Alternative therapy products are classified as 'dietary supplements,' according to the Dietary Supplement Health and Education Act of 1994 (DSHEA). In section 3 of DSHEA, a dietary supplement is defined as a product intended to supplement the diet and contains one or more of the following: a vitamin, a mineral, or an herb or other botanical or amino acid. According to section 4, these products are excluded from the regulatory approval of the Food and Drug Administration. It is the goal of this feature to provide a critical and unbiased evaluation of alternative therapy products.
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There is appropriate concern about the potential risk for hepatotoxicity from herbal products because they are unregulated and therefore not standardized with regard to their contents. This is particularly the case for the crude herbals that are commonly formulated as a mixture, so that their ingredients may be ambiguous and even contain harmful contaminants. Presented here is an overview of the more commonly recognized herbal products that have been reported to be associated with liver injury. Although many of them are clearly implicated, there are some, particularly those identified solely through an occasional case report, for which the relationship is uncertain.
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Most patients with rheumatic diseases experience difficulties with chronic pain. To assist clinicians in directly addressing this pain, this article presents a treatment approach and algorithm based on best evidence. The usual approach for mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate or poorly tolerated, and if there is an element of sleep loss, it is then reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial of one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate a trial of chronic opioid earlier. Cannabinoids and topicals may also be appropriate as single agents or in combination.
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Alternative medicine is used extensively by patients with chronic pain due to e.g., osteoarthritis. Only few of these drugs have be tested in a controlled setting and the present study was undertaken to examine the effect of ginger extract, one of the most popular herbal medications. Ginger extract was compared to placebo and Ibuprofen in patients with osteoarthritis of the hip or knee in a controlled, double blind, double dummy, cross-over study with a wash-out period of one week followed by three treatment periods in a randomized sequence, each of three weeks duration. Acetaminophen was used as rescue medication throughout the study. The study was conducted in accordance with Good Clinical Practice (European Guideline for GCP). A ranking of efficacy of the three treatment periods: Ibuprofen>ginger extract>placebo was found for visual analogue scale of pain (Friedman test: 24.65, P< 0.00001) and the Lequesne-index (Friedman test: 20.76, P< 0.00005). In the cross-over study, no significant difference between placebo and ginger extract could be demonstrated (Siegel-Castellan test), while explorative tests of differences in the first treatment period showed a better effect of both Ibuprofen and ginger extract than placebo (Chi-square, P< 0.05). There were no serious adverse events reported during the periods with active medications. In the present study a statistically significant effect of ginger extract could only be demonstrated by explorative statistical methods in the first period of treatment before cross-over, while a significant difference was not observed in the study as a whole.
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EF4 is an entirely new approach to the management of diabetic neuropathy. EF4 (providing gamma-linolenic acid or gamolenic acid, GLA) has been shown to reverse existing diabetic neuropathy in trials in seven centres. Diabetic animals and humans have a reduced ability to convert dietary linoleic acid to GLA. GLA and its metabolites are required for normal neuronal structure and function and a normal microcirculation. The lack of GLA and its metabolites may play a major role in the development of the neuropathy. EF4 helps to correct the biochemical defects, restores levels of GLA metabolites towards normal and produces highly significant clinical and neurophysiological improvements in diabetic neuropathy.
Article
Devil's Claw (Harpagophytum procumbens), an herbal product being marketed in Canada and in Europe as a home remedy for the relief of arthritic disease, was investigated in healthy humans on eicosanoid production during spontaneously blood clotting. Volunteers took H. procumbens (daily 4 capsules of 500 mg powder containing 3% of total glucoiridoids) for a period of 21 days. The following are the results (mean (SEM)): before H. procumbens intake, prostaglandin (PG)E2 (ng/ml serum): 2.1 (0.4) (n = 25), thromboxane (TX)B2: 147 (27) (n = 25), 6-keto-PGF1 alpha: 4.4 (0.7) (n = 13), leukotriene (LT)B4: 3.4 (0.4) (n = 25); after intake: PGE2: 3.2 (0.6), TXB2: 143 (24), 6-keto-PGF1 alpha: 4.2 (0.9), LTB4: 3.8 (0.6). Each subject serving as her own control, no statistically significant differences were observed between before and after H. procumbens intake. These results indicate that Devil's Claw lacks, at least in healthy humans and under the selected conditions, the biochemical effects on arachidonic acid metabolism of antiarthritic drugs of the non-steroidal antiinflammatory type.
Article
The dried aqueous extract of Harpagophytum procumbens (Pedaliaceae) and its main iridoid glycoside, harpagoside, have been evaluated for anti-inflammatory and analgesic effects in mice and rats, in order to validate or invalidate the involvement of this compound in such properties. This extract exerted significant and dose-dependent anti-inflammatory and analgesic effects, from the dose 100 mg of dried secondary roots/kg, the first being obtained on an acute inflammatory process (carrageenan-induced edema test in rats) and the second being obtained against a chemical stimulus (writhing test in mice). Harpagoside does not appear to be involved in anti-inflammatory properties, since this iridoid glycoside did not protect against carrageenan inflammatory effects when it was used at 5 and 10 mg/kg; 5 mg corresponding to the quantity contained in 400 mg of dried secondary roots. The main iridoid glycoside of H. procumbens appears to be implicated in the peripheral analgesic properties of this species, but other compounds have to be involved, since the dose of 10 mg/kg exerted a significant protective effect. The absence of the activity of H. procumbens after an acid treatment (0.1 N hydrochloric acid), similar to the physio-chemical conditions found in the stomach, suggests the use of a suitable galenic preparation in order to protect the active principles from the action of the acid released in the stomach.
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The rhizomes of Zingiber officinale (ginger) and Alpinia officinarum contain potent inhibitors against prostaglandin biosynthesizing enzyme (PG synthetase). Gingerols and diarylhepatanoids were identified as active compounds. Their possible mechanism of action which was deduced from the structures of active compounds indicated that the inhibitors would also be active against arachidonate 5-lipoxygenase, an enzyme of leukotriene (LT) biosynthesis. This was verified by testing their inhibitory effects on 5-lipoxygenase prepared from RBL-1 cells. A diarylheptanoid with catechol group was the most active compound against 5-lipoxygenase, while yakuchinone A was the most active against PG synthetase.
Article
The effects of capsaicin on the ability of platelets to aggregate in response to thrombin, platelet-activating factor or calcium ionophore (A23187) were examined. At concentrations previously shown to activate sensory afferent neurons, capsaicin markedly inhibited the responsiveness of platelets to the three agonists. The effects of capsaicin on platelet aggregation were reversible, and could be observed if capsaicin was added after platelets had begun to aggregate in response to the agonist. Capsaicin did not affect the shape change which occurs in response to the agonists, a process which is calcium-independent. These results demonstrate that capsaicin, at concentrations which are frequently used to 'selectively' activate sensory afferent neurons, is also capable of affecting the function of the platelet. Such non-specific effects of capsaicin must be considered when this substance is used as a pharmacological probe of sensory afferent nerve function.
Article
Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6g/day) and 21 received placebo (olive oil 6g/day). No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits.
Article
Tripterygium wilfordii Hook F (TWH) is a vine-like plant that grows in a wide area of south China. An alcohol extract of this plant known as T2 has been suggested to be effective in the treatment of rheumatoid arthritis (RA). To examine the mechanism by which this herbal remedy might be effective in RA, the capacity of T2 to alter human immune responsiveness in vitro was investigated. Human peripheral blood mononuclear cells were obtained from normal adults and separated into purified populations of monocytes, T cells, and B cells. T2 at 0.1-1 micrograms/ml inhibited antigen- and mitogen-stimulated proliferation of T cells and B cells, interleukin-2 (IL-2) production by T cells, and immunoglobulin production by B cells. T2 did not affect IL-2 receptor expression by T cells, IL-1 production by monocytes, or the capacity of monocytes to present antigen. Inhibition could not be accounted for by nonspecific toxicity. These results support the conclusion that T2 exerts a powerful suppressive effect on human immune responses. This action might account for its therapeutic effectiveness in RA.
Article
The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.
Article
Capsaicin application to human nasal mucosa was found to induce painful sensation, sneezing, and nasal secretion. All of these factors exhibit desensitization upon repeated applications. The acute effects induced by capsaicin (300 micrograms/100 microliters) application to the nasal mucosa were studied in healthy volunteers and cluster headache patients. These effects were not different in both nostrils of cluster headache patients as well as in the single nostril of healthy controls. Likewise, the time course of desensitization to the painful sensation and nasal secretion induced by capsaicin applied for five consecutive days in control subjects was almost superimposable to those observed in the nasal mucosa of cluster headache patients. The number of spontaneously occurring attacks was significantly reduced in the 60 days after the end of capsaicin treatment. Whether the beneficial effect induced by capsaicin application to the nasal mucosa could be ascribed to a specific action on sensory neurons remains unknown.
Article
The effects of 10 ml of evening primrose oil or olive oil, administered twice daily for 12 weeks, on clinical and laboratory signs and on plasma prostaglandins were studied in 18 patients with rheumatoid arthritis. The plasma concentration of PGE2 decreased and that of TxB2 increased in both treatment groups, but no significant improvement could be seen in either group.
Article
In Langendorff preparations of rat heart, hyperkinetic ventricular arrhythmias (HVA) have been induced by an ischaemic perfusion (coronary flux 0.5 ml/min; pressure 8 mmHg) and following reperfusion at basal conditions (coronary flux 8 ml/min; pressure 50 mmHg). Crude methanolic extracts of Harpagophytum procumbens secondary roots and harpagoside showed a significant, dose-dependent, protective action toward HVA induced by reperfusion.
Article
In conscious normotensive rats the dried crude methanolic extract of Harpagophytum procumbens secondary roots caused a significant dose-dependent reduction of arterial blood pressure. The decrease was significant only at higher doses given by gavage (dried extract = 400 mg/kg). At the same time a decrease of heart rate was observed. In the same experimental conditions, harpagoside presented an activity lower than doses of Harpagophytum procumbens extract containing corresponding quantities of harpagoside. In spontaneously beating Langendorff preparations of rabbit heart, the Harpagophytum procumbens methanolic extract caused a mild decrease in the heart rate with a concomitant mild positive inotropic effect at lower doses but a marked negative inotropic effect at higher doses. The coronary flow decreased at higher doses only. The negative chronotropic and positive inotropic effects of harpagoside were comparatively higher with respect to that of the extract, whereas harpagide had only a slight negative chronotropic effect and a considerable negative inotropic one. Both in experiments on intact rats and on isolated rabbit heart, the Harpagophytum procumbens extract also demonstrated a protective action with regard to arrhythmias induced by aconitine, and particularly to those provoked by calcium chloride and epinephrine--chloroform.
Article
Capsaicin was found to be a potent inhibitor of platelet aggregation and release reaction. It inhibited the aggregation of rat platelet induced by collagen and thrombin, but only slightly reduced those of AA and A23187. The IC50 on collagen-induced platelet aggregation was about 85 micrograms/ml. Less inhibition was observed in the aggregation of platelet-rich plasma. Increase of the calcium concentration could not overcome the inhibitory effect. Washing of the capsaicin-pretreated platelets only partially reversed the inhibition. Capsaicin also inhibited ATP release induced by thrombin and A23187 in the presence of EDTA. MDA and TXB2 formation were markedly inhibited by capsaicin in platelets challenged by collagen, thrombin and A23187. In AA-stimulated platelets, MDA formation was slightly decreased and TXB2 formation was not affected. Capsaicin showed more marked inhibition in the presence of CP/CPK, indomethacin or a combination of both. Capsaicin reduced the hemolysis of RBCs induced by hydrogen peroxide or hypotonicity. It was concluded that capsaicin had some membrane stabilizing property and this might lead to the interference of the activation of phospholipase A2.
Article
Feverfew has been used since antiquity to treat fevers and other inflammatory conditions. Feverfew extracts were found to inhibit ADP, thrombin, or collagen-induced aggregation of human platelets, but significantly, did not affect aggregation induced by arachidonic acid. Synthesis of thromboxane B2 from exogenous 14C-arachidonic acid was also not inhibited. Washed platelets prelabelled with 14C-AA responded normally to thrombin by releasing 14C-TXB2. This was completely blocked by feverfew. A purified platelet phospholipase A2 was inhibited by the material with an I50 of 0.1 antiplatelet units. The pharmacological properties of feverfew may thus be due to an inhibitor of cellular phospholipases, which prevents release of arachidonic acid in response to appropriate physiological stimuli.
Article
Capsicum, a hot appetizer and seasoning, has been found to induce increased fibrinolytic activity and simultaneously cause hypocoagulability of blood when ingested or when retained in the mouth for a short time. The effect on fibrinolysis and blood coagulation of capsicum can be reproduced in the same subjects within a short time after the first stimulation. More investigations on this effect may lead to the discovery of some ideal drugs for both treatment and prevention of thromboembolism. Fibrinolytic activity measured by euglobulin lysis time in 88 Thai subjects (mean +/- SD = 167 +/- 66.84 min) was significantly higher than in 55 American whites (mean +/- SD = 254 +/- 126.70 min) residing in Thailand for a period of time (p less than 0.001). The Thai people consume capsicum with their meals. Their fibrinolytic activity, therefore, is activated several times during the day and this activation could be an important factor in causing high fibrinolytic activity. This customary habit of food ingestion is very likely a factor contributing to the racial difference in fibrinolysis. Furthermore, the Thais also have lower plasma fibrinogen and higher antithrombin III compared to Americans. These could certainly be additional factors, in addition to fibrinolytic activity, that play a role in the rarity of thromboembolism among Thais.
Article
It has been reported that gamma-linolenic acid (GLA)-rich diets suppress mammary carcinogenesis and transplanted tumor growth and that GLA inhibits the growth of cultured human cancer cell lines. We compared the effects of dietary GLA and linoleic acid (LA) on the growth of MDA-MB-435 human breast cancer cells and their expression of the metastatic phenotype in vivo and in vitro. Athymic nude mice (30/dietary group) were fed isocaloric diets containing 20% (wt/wt) fat but providing 8% GLA or LA for 7 days, and 10(6) tumor cells were then injected into a thoracic mammary fat pad. The diets were continued for a further 11 weeks. The primary tumor growth rates were similar in mice from the two dietary groups; there was a nonstatistically significant trend for the incidence of macroscopic lung metastases and the total lung metastatic volumes to be higher in the GLA-fed mice (79% and 40.1 +/- 13.9 mm3) than in the LA-fed mice (64% and 15.5 +/- 5.4 mm3). The tumor cell phospholipids from the 8% GLA-fed mice contained significantly lower LA levels but higher arachidonic acid levels (both p < 0.001) than those from 8% LA-fed mice. Also the arachidonate-derived eicosanoids (prostaglandin E, leukotriene B4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids) were significantly higher in tumors from the 8% GLA group. Zymography showed higher 92-kDa type IV collagenase activity in tumors from 8% GLA-fed mice. In vitro, GLA and LA, at 0.5-2 micrograms/ml, stimulated MDA-MB-435 cell growth; 10 micrograms/ml was mildly inhibitory. Whereas LA stimulated tumor cell invasion and 92-kDa type IV collagenase production in vitro, GLA inhibited invasion and did not induce activity of the proteolytic enzyme. Our results do not support the hypothesis that supplementation with GLA would exert a beneficial effect on the progression of an existing breast cancer, perhaps because it is metabolized in vivo to arachidonate-derived eicosanoids that are known to be involved in the metastatic process.
Article
Tripterygium wilfordii Hook F (TWHF) is a kind of Chinese herbal medicine used for 2000 years. It was applied externally for treatment of arthritis and inflammatory tissue swelling in early years. Recently, this drug has been found to have immunosuppressive effects which could successfully induce remission of some autoimmune disorders without obvious adverse effects. Although there are side effects of gastrointestinal upset, infertility and suppression of lymphocyte proliferation, little information about lethal toxicities has been reported. A case is presented here of a previously healthy young man who developed profuse vomiting and diarrhea, leukopenia, renal failure, profound hypotension and shock after ingestion of an extract of TWHF. In addition to his hypovolemic shock, serial electrocardiograms (ECG), cardiac enzyme studies, and echocardiography also showed some evidence of coexisting cardiac damage. He died of intractable shock 3 days after the abuse of TWHF. Further studies of the pathogenesis of peripheral collapse and possible cardiac toxicity, and determination of the therapeutic range of this drug are necessary before it is used extensively.
Article
Effects of capsaicin on autonomic nerves in the nasal mucosa and olfactory bulb of toluene diisocyanate sensitized guinea pigs were studied using immunocytochemistry. In the nasal mucosa, substance P (SP)- and tyrosine hydroxylase (TH)-like immunoreactive (SPI and THI) fibers seemed to decrease after capsaicin application. Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers did not show obvious alterations. In the olfactory bulb, SPI and CGRPI fibers were few and the effects of capsaicin on those fibers were difficult to evaluate. THI fibers seemed not to be affected by capsaicin. It is suggested that capsaicin affects not only sensory nerves but that it also impacts on THI sympathetic nerves in the nasal mucosa.
Article
"Hunan hand" is a contact dermatitis resulting from the direct handling of chili peppers containing capsaicin. Capsaicin also is found in an over-the-counter topical agent for treatment of postherpetic neuralgia, diabetic neuropathy, and arthritis. We present the case of a patient with capsaicin-induced dermatitis and discuss the pathophysiology, therapy, and current uses of capsaicin. [Williams SR, Clark RF, Dunford JV: Contact dermatitis associated with capsaicin: Hunan hand syndrome. Ann Emerg Med May 1995;25:713-715.].
Article
The discovery of the reversible antifertility action of an extract from Tripterygium wilfordii both in male rats and in men in 1986 stimulated worldwide interest. International and national collaborations aimed at the bioassay-directed sub-fractionation of materials extracted from the plant was then organized and to date, a series of six male antifertility diterpene epoxides have been isolated. Their chemical structures have been identified and found to be triptolide, tripdiolide, triptolidenol, tripchlorolide, 16-hydroxytriptolide and T7/19 (structure not yet published). At the ED95 dosage levels, they act mainly on metamorphosing spermatids and testicular and epdidymal spermatozoa with exfoliation and inhibition of basic nuclear protein turnover of late spermatids, delayed spermiation and sperm head-tail separation and microtubule, microfilament and membrane damages. A preliminary toxic evaluation indicated that these compounds were immunosuppressive at dose levels 5-12 times their antifertility doses. Immuno-suppression is an important weakness for an antifertility agent, but if the immuno-suppressive dose of a drug is much higher than its antifertility dose, it could yet be regarded as a safe contraceptive. Therefore, in the safety evaluation of compounds isolated from Tripterygium wilfordii, it warrants our attention to probe deeply into their precise dose/immuno-effect relationship.
Article
Effects of a dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs) linoleic and gamma-linolenic acids (GLA) on blood lipids, platelet function, and vascular prostacyclin production were studied 12 hyperlipidemic patients (doses of 3 g/day) and 12 male Wistar rats (doses of 3 mg/kg/day) for 4 months. In humans, GLA supplementation decreased plasma triglyceride (TG) levels by 48% (p < 0.001) and increased HDL-cholesterol concentration by 22% (p < 0.01). Total cholesterol and LDL-cholesterol levels were significantly decreased by omega-6 EFAs. Platelet aggregation induced by low concentrations of adenosine diphosphate (ADP) and epinephrine, and serum thromboxane B2 decreased by 45% both in humans and animals after GLA supplementation. Bleeding time increased 40% (p , 0.01). In rats, vascular prostacyclin production measured by radioimmunoassay of 6-keto-PGF1 alpha was enhanced by GLA intake. These effects of omega-6 EFAs may contribute to cardiovascular protection and prevention of the atherosclerotic disease.
Article
A variety of preparations of Tripterygium wilfordii Hook.F (TWHF) have been reported to be effective in the treatment of autoimmune diseases, including a chloroform methanol extract termed T2 and an ethyl acetate (EA) extract. The immunosuppressive activity of the EA extract was analyzed and the components accounting for this effect determined and compared to those of T2. More than 0.25 microgram/ml of the EA extract inhibited antigen- and mitogen-stimulated human T cell proliferation. The inhibitory effect of the EA extract on T cell proliferation resulted largely from suppression of interleukin-2 production. At concentrations that inhibited T cell function, the EA extract also profoundly suppressed [3H]-thymidine incorporation by mitogen-stimulated B cells, but it did not inhibit antigen presentation by monocytes and only modestly affected interleukin-6 production by lipopolysaccharide-stimulated monocytes. The profile of inhibition was comparable to that previously reported for the chloroform-methanol extract of Tripterygium wilfordii Hook.F, T2. To delineate the components of these extracts that might account for their immunosuppressive effect, we analyzed the composition of diterpenoid compounds. Both extracts contained triptolide and tripdiolide as the major immunosuppressive diterpenoids, but at different concentrations. Comparison of the composition of these extracts and the inhibitory capacity of the purified components indicated that the triptolide concentration of the EA extract can account for its immunosuppressive activity, although the combination of both triptolide and tripdiolide or other unknown components may be necessary to explain the inhibitory effects of T2.
Article
The aim of the present study was to determine the frequency and amount of chili taken by peptic ulcer patients and control subjects. One hundred three Chinese patients with peptic ulcer and 87 control patients were interviewed using a standard questionnaire. Those subjects who deliberately avoided chili use because of symptoms or advice from friends or medical practitioners were excluded. The median number of times of chili use per month was eight in the ulcer group (25-75% quartiles 1-30) compared to 24 (8-56) in the control group (P < 0.001). The median amount of chili used per month was 312 units (25-75% quartiles 38-899) in the ulcer group compared to 834 units (274-1892) in the control group (P < 0.001). The odds ratio of having peptic ulcer disease, adjusted for age, sex, analgesic use, and smoking by multiple logistic regression, was 0.47 (95% confidence intervals: 0.25-0.89) for subjects who had a higher intake of chili both in terms of frequency as well as amount used compared to those who took less chili. Our data support the hypothesis that chili use has a protective effect against peptic ulcer disease.
Article
The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil (BCSO), in a randomized, double-blind, placebo controlled, 24-week trial in patients with RA and active synovitis. BCSO is rich in gammalinolenic acid (GLA) and alphalinolenic acid (ALA). Both GLA and eicosapentaenoic acid which derives from ALA suppress inflammation and joint tissue injury in animal models. Treatment with BCSO resulted in reduction in signs and symptoms of disease activity in patients with RA (P < 0.05). In contrast, patients given a placebo showed no change in disease. Overall clinical responses (significant change in four measures) were no better in the treatment group than in the placebo group. No patients withdrew from BCSO treatment because of adverse reactions. However, many patients withdrew because BCSO and its placebo had to be administered in 15 large capsules daily. Nonetheless, the study indicates that BCSO is a potentially effective treatment for active RA. However, means must be found to reduce the size and number of capsules taken, so that larger studies of longer duration in RA patients can be done.
Article
We have studied the effects of a chloroform extract of fresh leaves from the herb feverfew (Tanacetum parthenium) on potassium currents in smooth muscle. The currents were recorded from single cells dissociated from the rat anococcygeus and the rabbit ear artery using the whole-cell patch-clamp technique. When applied to cells isolated from the rat anococcygeus, the extract reduced the inactivating voltage-dependent potassium current in a concentration-related manner, with an IC50 value (the concentration that reduced the current by 50%) of 56 micrograms mL-1. Complete block of the current occurred at 1 mg mL-1. In addition to reducing the peak current, feverfew decreased the time to peak of the current and increased the rate of decay of the current. These effects can be explained by the feverfew extract blocking open potassium channels. In single cells isolated from rabbit ear artery the feverfew extract again reduced the voltage-dependent potassium current, whilst at the same time having no effect on the spontaneous transient outward currents which arise as a consequence of activation of calcium-dependent potassium channels. These results suggest that chloroform extracts of feverfew leaf contain an as yet unidentified substance capable of producing a selective, open-channel block of voltage-dependent potassium channels.
Article
A substantial disturbance of the metabolism of the n-6 essential fatty acids (EFAs) exists in both human and experimental diabetes mellitus. The process of conversion of dietary linoleic acid to gammalinolenic, dihomogammalinolenic and arachidonic acids, and other polyunsaturates is inadequate in diabetic patients. Disturbances of these EFAs and the 1- and 2-series prostaglandins derived from them cause a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia. This will in turn produce an escalating cycle of further hypoxia through the generation of oxygen-free radicals and aggravation of neural capillary endothelial damage. Endoneurial hypoxia impairs axonal transport, produces demyelination, and reduces neural ATP-ase activity. Furthermore, depletion of polyunsaturated fatty acids derived from n-6 pathway may lead to abnormalities of myelin turnover, membrane-bound proteins (such as enzymes and receptors) and other axonal structural abnormalities. The disorders postulated here may synergistically interact with the metabolic changes described in both the glycosylation and the myoinositol hypotheses and may have important implications in the approach to treat diabetic neuropathy.
Article
1. Kallidin (5-500 nmol), hypertonic saline (0.9-20% NaCl) or low pH medium (citric acid: pH 2.5-1) applied (50 microliters) to the human nasal mucosa produced a pain response (evaluated by a visual analogue scale) that was related to the concentration of the peptide, NaCl or hydrogen ions, respectively. 2. Application (50 microliters) of capsaicin (50 nmol) to the human nasal mucosa produced overt pain. After repeated administrations (once a day for 5-7 days) to one nostril this effect underwent almost complete desensitization, while in the contralateral nostril, treated with the vehicle, the response to capsaicin was unaffected. 3. The pain response produced in the human nasal mucosa by topical application (50 microliters) or kallidin (50-500 nmol), NaCl (10-20%) or citric acid (pH 1.5-1) solutions was then studied before and after local capsaicin desensitization. 4. The pain response to pH 1.5 or 1 citric acid was markedly reduced (by 60% and 75%, respectively) in the capsaicin-treated nostril. However, the pain response to 10% or 20% NaCl or the mild pain response to 50 or 500 nmol kallidin were unaffected by capsaicin pre-treatment. 5. The present results suggest that prolonged topical capsaicin treatment to the human nasal mucosa may lead to selective desensitization to certain algesic stimuli such as capsaicin itself and hydrogen ions.
Article
Mutagenic and antimutagenic activities of extracts and chromatographic fractions of Uncaria tomentosa bark are reported. The plant extracts and fractions show no mutagenic effect in different strains of Salmonella typhimurium with and without metabolic activation. However, the plant extracts and fractions show a protective antimutagenic effect in vitro against photomutagenesis induced by 8-methoxy-psoralen (8-MOP) plus UVA in S. typhimurium TA 102. A decoction of U. tomentosa ingested daily for 15 days by a smoker decreased the mutagenicity induced in S. typhimurium TA98 and TA100 by the subject's urine.
Article
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.
Article
A survey of the Mayan pharmacopoeia revealed that tissues of Capsicum species (Solanaceae) are included in a number of herbal remedies for a variety of ailments of probable microbial origin. Using a filter disk assay, plain and heated aqueous extracts from fresh Capsicum annuum, Capsicum baccatum, Capsicum chinese, Capsicum frutescens, and Capsicum pubescens varieties were tested for their antimicrobial effects with fifteen bacterial species and one yeast species. Two pungent compounds found in Capsicum species (capsaicin and dihydrocapsaicin) were also tested for their anti-microbial effects. The plain and heated extracts were found to exhibit varying degrees of inhibition against Bacillus cereus, Bacillus subtilis, Clostridium sporogenes, Clostridium tetani, and Streptococcus pyogenes.
Article
Systemic sclerosis is a multi system disorder, for which there is no satisfactory treatment. Theoretically, dietary supplementation with essential fatty acids may lead to an increase in their derivatives, the vasoactive prostaglandins, which benefit the acute and chronic ischaemic lesions of this disease. We assessed the value of concentrated essential fatty acids in patients with systemic sclerosis, concentrating particularly on vascular symptoms and objective tests of vascular reactivity. Twenty-five patients with systemic sclerosis were randomised to receive concentrated essential fatty acids or placebo, for 6 months in a double-blind parallel group study. There was no significant difference between the active and placebo groups in terms of maximum blood flow after warming, minimum blood flow after cooling or the recovery time after cooling. There were no significant differences between the groups in the other parameters measured. Dietary essential fatty acids have no role in the treatment of vascular symptoms in established systemic sclerosis.
Article
Pharmacokinetics and metabolism of theophylline were studied in three groups of male rabbits, after intravenous administration (12 mg/kg), with and without oral groundCapsicum fruit suspension. Compared with control values, plasma theophylline half-life of distribution and of elimination, areas under plasma curves, clearance and volume of distribution did not show any significant difference. On the contrary, the elimination rate constant (k1,0) is significantly different (0.01<P<0.05) after a single dose of capsicum and remained unchanged after a repeated dose. Concerning the metabolism of theophylline in rabbits, the results showed that the oral administration of a single dose ofCapsicum fruit suspension does not significantly affect the urinary excretion of theophylline and its metabolites — 1,3-dimethyluric acid (1,3-DMU) and 1-methyluric acid (1-MU). On the other hand, after a repeated dose ofCapsicum fruit for 7 days, the quantity of 1-MU was significantly reduced (0.01<P<0.05). In conclusion, it was found that a single dose ofCapsicum fruit could affect pharmacokinetic parameters of theophylline (k1,0), while a repeated dose affected the metabolic pathway of xanthine oxidase.
Article
This case report of camphor ingestion in a 15-month-old child illustrates the potential toxicity of a common household product. Details of the patient presentation are reported along with a review of the literature. Patient information was collected using the records of Poison Control, the Emergency Department, and the Health Records at the Hospital for Sick Children in Toronto, Ontario, Canada. A comprehensive review of the literature was conducted using the MEDLINE database for the time period 1966 to April 1995. Oral ingestion of camphor is unusual, given that these products have both unpleasant taste and texture. This patient ingested 70 ml of an over-the-counter medicated ointment containing 4.73% camphor, 2.6% menthol, and 1.2% eucalyptus oil. While the concentration of camphor in this product is low, an estimated 280 mg/kg of camphor was consumed. With significant ingestion of camphor (> 50 mg/kg), neurologic toxicity is common. In this patient, prolonged generalized tonic-clonic seizure activity was noted approximately two hours post single acute ingestion of camphor. This delay in onset of seizure activity is atypical, as seizures have previously been noted to occur in the 90 minutes following ingestion. Readily available medicated ointments containing camphor have potential for serious or fatal consequences when ingested by children.