7. งาน pharmacological capsaicinoids7.1. ในการรักษาอาการปวดIt has been shown that the topical application of capsaicin can alleviate the pain sensations by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system (CNS). In various parts of the world, the leaves and fruits of Capsicum are reported to have application in treating painful menses (Dominican Republic: Estévez and Báez, 1998; Palestine: Jaradat, 2005; Eastern Nicaragua: Coe, 2008; Taiwan and the Batanes Islands: Yamamoto and Nawata, 2009; Dek Island, Ethiopia: Teklehaymanot, 2009; Eastern foothills of the Andes: Jernigan, 2009; Peru: Valadeau et al., 2010) whereas its application in treating toothache and muscle pain is also well documented (Bhagowati and Changkija, 2009). A recent ethno medicinal survey conducted by Rout and Panda (2010) also revealed that the fruits of Capsicum frutescens are used to alleviate waist pain in the villages of Mayurbhanj district of Orissa, India. Capsaicin has been shown to be a potent agonist for the transient receptor potential channel, vanilloid type 1 (TRPV1). The non-selective, ligand gated ion channel vanilloid receptor is predominantly expressed on the peripheral and central terminals of primary sensory neurons (nociceptors) located in the dorsal root, trigeminal, and nodose ganglia (Caterina and Julius, 2001) where it plays a key role in the detection of noxious stimuli that may result in tissue damage (Westaway, 2007). It has attracted the attention of several researchers ranging from the pharma industry to the academic community for its potential exploitation in a number of therapeutic areas, particularly the alleviation of chronic pain states. The topical application of capsaicin cream, although initially produces an uncomfortable burning sensation, eventually leads to analgesia due to the persistently high intracellular Ca2+ levels that subsequently desensitize the nociceptor fibers causing degeneration of the pain signalling pathway (Butera, 2007). There are growing evidences to suggest that TRPV1 is also expressed in brain, in the gastrointestinal (GI) system, lung, and bladder (Butera, 2007). In fact, capsaicin and its ultrapotent analogue resiniferatoxin have been tried on an empirical basis in diverse disease states ranging from chronic intractable pain through vasomotor rhinitis to the overactive bladder (Szallasi and Blumberg, 1999). Topical creams with capsaicin are used to treat pain from postherapeutic neuralgia and diabetic neuropathy (0.075% cream 3–4 times daily for eight weeks), osteoarthritis (0.025% cream four times daily), and rheumatoid arthritis (Reynolds, 1999; Anon., 2003). Capsaicin has also been used to treat pain due to pruritus, psoriasis, mastectomy, bladder disorders and clusterheadaches(Reynolds,1999).Ameta-analysisofrandomized controlled trials for determining the efficacy of topical capsaicin in the treatment of chronic pain from neuropathic and musculoskeletal disorders and adverse events and withdrawals revealed that although topically applied capsaicin has moderate to poor efficacy, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of other treatments (Mason et al., 2004). Although, these scientific reports support the traditional use of Naga chilli in northeastern India in treating pain, yet the variation in the results of pharmacological studies with regard to the dose, animals and experimental conditions has raised the concerns for the safe use of capsaicin and its derivatives as analgesic drug of the future. The use of capsaicin as analgesic can be counterproductive in the diabetic patients who are already prone to developing necrosis (Szallasi and Appendino, 2004).7.2. ผลกระทบต่อการควบคุมอุณหภูมิของร่างกายAlthough, in ethnomedicinal literature, we could not find any direct evidence of using chilli in body temperature regulation, it was observed that the people living in tropical climates eat their food more hot compared to those living in temperate climates in order to combat the warm climate by gustatory sweating (Lee, 1954). Certainly, the capsaicin receptor is activated both by capsaicin and heat, indicating a possible role in thermoregulation. Transient receptor potential (TRP) cation channels are suggested to be critical for the external thermal stimuli of the body. Among the various types of TRPs, four channels (TRPV1–4), appear to account for detection of warm (TRPV3 and TRPV4), or painfully hot (TRPV1, ≥42◦C; TRPV2, ≥52◦C) temperatures (Montell and Caterina, 2007). It has been convincingly demonstrated that TRPV1 participates in the regulation of body temperature (Steiner et al., 2007; SharifNaeini et al., 2008). Steiner et al. (2007) used a highly specific and potent TRPV1 antagonist, AMG0347, which inhibits in vitro expressed TRPV1 with an IC50 of <1nM, regardless of whether the channel is activated by heat, capsaicin or low pH. In addition, Gavva et al. (2007) by conducting experiments on multiple species (rats, dogs and monkeys) established that TRPV1 function in thermoregulation is conserved from rodents to primates. This study also suggested that TRPV1 appears to be tonically activatedviaamodeotherthanthroughthermalstimulation.However, the nature of this activation mechanism is not known. It would be therefore, worthwhile to explore further the broader role of TRP channels in regulation of body temperature. Also, from the physiological point of view capsaicin is perhaps one of the most enigmatic deterrent molecules ever produced by plants (Nagy et al., 2004) and is a potent agonist for TRPV1. Although capsaicin has long been known to decrease body temperature (hypothermia)inmultiplespecies,includinghumans(Hori,1984;Szallasiand Blumberg, 1999), there are contradictory reports available for different organisms. Kobayashi et al. (1998) performed an experiment using male Wistar rats where capsaicin (5mgkg−1) was administered subcutaneously. Their results led to the conclusion that capsaicin stimulates the systems regulating heat loss and heat production simultaneously and independently, such that they have no reciprocal inhibition. This was further explained by Lee et al. (2000a) suggesting that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and the body temperature regulation is performed without an integrative centre. On the other hand, in humans, researchers observed that people given a cayenne supplement before exposure to a temperature of 38◦C had lower skin temperature than those consuming the placebo (Nelson, 2000).มีการบันทึกกันกลไกสอง capsaicininduced hypothermia กลไกที่แท้จริงของสาร P และรุ่นเพปไทด์ที่เกี่ยวข้องกับยีน calcitonin (Jhamandas et al., 1984 Holzer, 1991 Gavva et al., 2005), ซึ่งเกิด vasodilation ในยสปริง และสูญเสียความร้อนที่เพิ่มขึ้นดังนั้น และกลไกที่สองลดการเผาผลาญ (เป็นวัด โดยการลดปริมาณการใช้ออกซิเจน), ซึ่งช่วยลดความร้อนผลิต (Hori, 1984) ในการทดลองอื่น 6 หนุ่มสุขภาพคนกิน Tabasco ร้อนน้ำเย็นมีอุณหภูมิร่างกายสูงขึ้นในระหว่างรอบปแรก ทำให้ยากสำหรับพวกเขา การหลับ และ การนอนหลับที่ดี (เอ็ดเวิร์ด et al., 1992) รายงานเหล่านี้แนะนำสำคัญผลของแคปไซซินควบคุมอุณหภูมิของร่างกาย อย่างไรก็ตาม กลไกพื้นฐานซับซ้อนมาก และต้องการเพิ่มเติมเพื่อขุดผลของแคปไซซินในการควบคุมอุณหภูมิของร่างกายทั้งหมด7.3. ในการรักษาป้องกันโรคอ้วนCapsaicin has received increased attention for its anti-obesity effect. Red pepper consumption was reported to increase energy expenditure, lipid oxidation (Yoshioka et al., 1998) as well as decrease appetite (Belza et al., 2007). In another study, the addition of 30mg capsaicin to a high-fat breakfast and a high-carbohydrate breakfast significantly decreased prospective food consumption at lunch. Moreover, desire to eat as well as hunger significantly decreased after the high-fat breakfast with capsaicin (Yoshioka et al., 1999). Ahuja et al. (2006) reported the findings of a small human trial (on 36 people including 22 women, average BMI 26.3kg/m2), which showed that regular consumption of a chilli-containing meal could improve insulin control by about 60%. The ratio of C-peptide to insulin, a measure of insulin clearance, was also significantly improved during the chilli diet regime. Their results indicated that the habitual consumption of chilli may also be useful in ameliorating meal-induced hyperinsulinemia. A more recent study on the effects of novel capsaicinoid treatment on obesity and energy metabolism in humans concluded that treatment with 6mg/day capsaicinoid orally appeared to be safe, well tolerated and was associated with the loss of abdominal fat. Capsaicinoid ingestion was associated with a significant increase in fat oxidation (Snitker et al., 2009). Another study revealed that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing the inflammatory responses but also by enhancing the fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. Several different mechanisms have been proposed for the anti-obesity effectofcapsaicin.Theeffectsofcapsaicininadiposetissueandliver are related to its dual action on peroxisome proliferator activated receptor (PPAR) alpha and TRPV-1 expression/activation (Kang et al., 2009). The effects of capsaicin on energy and lipid metabolism areattributedtoanincreaseinsympatheticnervoussystemactivity (Yoshioka et al., 1998, 1999), increased blood flow and secretion in the gastrointestinal tract (Chen et al., 1992), and stimulation in sensory neurons resulting into increased noradrenaline levels (Belza et al., 2007). ). In an in viv
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