The hyperthermic effect of central cholecystokinin is mediated by the cyclooxygenase-2 pathway.

Cholecystokinin (CCK) increases core body temperature via CCK2 receptors when administered intracerebroventricularly (icv). The mechanisms of CCK-induced hyperthermia are unknown, and it is also unknown whether CCK contributes to the fever response to systemic inflammation. We studied the interaction between central CCK signaling and the cyclooxygenase (COX) pathway. Body temperature was measured in adult male Wistar rats pretreated with intraperitoneal infusion of the nonselective COX enzyme inhibitor metamizol (120 mg/kg) or a selective COX-2 inhibitor, meloxicam, or etoricoxib (10 mg/kg for both) and, 30 min later, treated with intracerebroventricular CCK (1.7 µg/kg). In separate experiments, CCK-induced neuronal activation (with and without COX inhibition) was studied in thermoregulation- and feeding-related nuclei with c-Fos immunohistochemistry. CCK increased body temperature by ∼0.4°C from 10 min postinfusion, which was attenuated by metamizol. CCK reduced the number of c-Fos-positive cells in the median preoptic area (by ∼70%) but increased it in the dorsal hypothalamic area and in the rostral raphe pallidus (by ∼50% in both); all these changes were completely blocked with metamizol. In contrast, CCK-induced satiety and neuronal activation in the ventromedial hypothalamus were not influenced by metamizol. CCK-induced hyperthermia was also completely blocked with both selective COX-2 inhibitors studied. Finally, the CCK2 receptor antagonist YM022 (10 µg/kg icv) attenuated the late phases of fever induced by bacterial lipopolysaccharide (10 µg/kg; intravenously). We conclude that centrally administered CCK causes hyperthermia through changes in the activity of "classical" thermoeffector pathways and that the activation of COX-2 is required for the development of this response.NEW & NOTEWORTHY An association between central cholecystokinin signaling and the cyclooxygenase-prostaglandin E pathway has been proposed but remained poorly understood. We show that the hyperthermic response to the central administration of cholecystokinin alters the neuronal activity within efferent thermoeffector pathways and that these effects are fully blocked by the inhibition of cyclooxygenase. We also show that the activation of cyclooxygenase-2 is required for the hyperthermic effect of cholecystokinin and that cholecystokinin is a modulator of endotoxin-induced fever.

Physiological and thermoregulatory effects of oral taurine supplementation on exercise tolerance during forced convective cooling.

AbstractWe investigated the effects of taurine supplementation on cycling time to exhaustion in cold conditions. Eleven males cycled to exhaustion at a power output equivalent to the mid-point between ventilatory threshold and maximum aerobic power following 15-min rest in the cold (apparent temperature of ∼ 4°C; air flow of 4.17 m s-1). Two hours before, participants ingested taurine (50 mg·kg-1) or placebo beverage. Pulmonary gases, carbohydrate (CHO) and fat oxidation, body temperatures, mean local sweat rate, heart rate, rate of perceived exertion (RPE) and thermal comfort were recorded. Time to exhaustion was not different between trials (taurine = 14.6 ± 4.7 min; placebo = 13.4 ± 5.6 min, P = 0.061, d = 0.27). There were no effects (P > 0.05) of taurine on core temperature, mean skin temperature or local sweat rates. However, the placebo condition showed greater (P < 0.05) reductions in arm-to-finger temperature gradient (i.e. vasodilation) across pre-exercise passive cold exposure and increased CHO oxidation (P < 0.05). Participants also reached a thermally 'comfortable' level quicker in the taurine condition (P < 0.05). A 50 mg·kg-1 dose of taurine did not statistically benefit endurance exercise after moderate cold exposure but conferred some potential vascular and metabolic effects.

Creatine Monohydrate Supplementation Increases White Adipose Tissue Mitochondrial Markers in Male and Female Rats in a Depot Specific Manner.

White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific stimuli. Non-shivering thermogenesis was previously thought to be uncoupling protein 1 (UCP1)-dependent however, recent evidence suggests that UCP1-independent mechanisms of thermogenesis exist. Namely, futile creatine cycling has been identified as a contributor to WAT thermogenesis. The purpose of this study was to examine the efficacy of creatine supplementation to alter mitochondrial markers as well as adipocyte size and multilocularity in inguinal (iWAT), gonadal (gWAT), and BAT. Thirty-two male and female Sprague-Dawley rats were treated with varying doses (0 g/L, 2.5 g/L, 5 g/L, and 10 g/L) of creatine monohydrate for 8 weeks. We demonstrate that mitochondrial markers respond in a sex and depot specific manner. In iWAT, female rats displayed significant increases in COXIV, PDH-E1alpha, and cytochrome C protein content. Male rats exhibited gWAT specific increases in COXIV and PDH-E1alpha protein content. This study supports creatine supplementation as a potential method of UCP1-independant thermogenesis and highlights the importance of taking a sex-specific approach when examining the efficacy of browning therapeutics in future research.

Thermoregulatory effects of guava leaf extract-menthol toner application for post-exercise use.

CONTEXT: Psidium guajava L. (Myrtaceae) leaf contains a wide variety of bioactive compounds that contribute valuable effects on human well-being. OBJECTIVE: This study investigates the influence of guava leaf extract-menthol toner on thermoregulation, including perspiration, skin temperature, and recovery heart rate. MATERIALS AND METHODS: This randomised, placebo-controlled clinical trial assessed the effects of the guava leaf extract-menthol toner and placebo with a 1-week washout period. Sixty-four participants were enrolled. The participants exercised on a treadmill until a 75% heart rate reserve was achieved for 5 min, followed by a 5 min post-exercise rest period. The skin temperature and heart rate were then measured before 5 mL of the testing product was sprayed to specific areas of the body, left it for 30 sec before wiped off. Post-exercise perspiration and skin temperatures were collected by sweat patches and measured by the Skin-thermometer ST500, respectively. A 20 min heart rate monitoring period started 10 min after the exercise and measured every 2 min intervals. RESULTS: Use of the toner significantly reduced post-exercise perspiration to approximately half of the baseline and placebo use values (p < 0.05). Furthermore, relative heart rate changes showed no significant differences among the tests (p > 0.05). Skin temperature was also unaffected (p > 0.05). DISCUSSION AND CONCLUSION: Guava leaf extract-menthol toner reduced perspiration by astringent effects but did not influence heat dissipation and did not affect cardiovascular mechanism compared to the controls. Additional cleaning with guava leaf extract-menthol toner could offer better hygiene after a workout.

Study on the experimental verification and regulatory mechanism of Rougui-Ganjiang herb-pair for the actions of thermogenesis in brown adipose tissue based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Rougui) has character of xin、gan、wen, belongs to Jing of heart、lung、bladder, and has the effect of dispersing cold and relieving pain. It is widely used to resolve the exterior and dissipate cold in Treatise on Febrile Diseases (Shang Han Lun), such as Chaihu Guizhi Ganjiang Tang and Guizhi Renshen Tang. Both these two prescriptions contain Cinnamomum cassia Presl and Zingiber officinale Rosc (Ganjiang). Rougui-Ganjiang herb-pair (RGHP) can warm viscera and remove cold, which is widely used in Shang Han Lun. And in modern times, recent studies have showed that cinnamon and ginger also have the effect of thermogenesis and regulating the body temperature, respectively. AIM OF THE STUDY: To maintain the body thermal homeostasis and prevent cold invasion of main organs, in this study, we assessed the underlying physiological changes induced by RGHP in mice exposed to -20 °C and explored the mechanisms for the thermogenic actions of RGHP in brown adipose tissue (BAT) by network pharmacology and molecular docking. MATERIALS AND METHODS: Male Kunming (KM) mice were fed normal diet with orally administration of distilled water or ethanol RGHP extract (three doses: 375,750 and 1500 mg/kg) for 21 days, once per day and then exposed to -20 °C for 2 h. The core temperature, activity ability and the degree of frostbite in mice, morphological and ATP content of adipocytes were measured. In addition, the network pharmacology was employed to predict the targets of RGHP' s thermogenesis effect on BAT. Pathway analysis and biological process with key genes was carried out through KEGG and GO analysis, respectively. Furthermore, the core ingredients and targets obtained by network pharmacology were verified by molecular docking and Western blot assays. RESULTS: RGHP can significantly increase the core body temperature, reduce the degree of frostbite and enhance the activity ability of mice after cold exposure. Meanwhile, it can also improve the lipid morphology and decrease ATP production in BAT. A network pharmacology-based analysis identified 246 ingredients from RGHP (two herbs), which related to 222 target genes. There were 8 common genes between 222 compounds target genes and 62 thermogenesis associated target genes, which linked to 49 potential compounds. There are 24 ingredients which degree are greater than the average. Among them, we found that oleic acid, EIC, 6-gingerol, eugenol, isohomogenol and sitogluside could be detected in mice plasma. The cAMP-PPAR signaling pathway was enriched for thermogenesis after KEGG analysis with 8 genes. Molecular docking analysis and Western blot assay further confirmed that oleic acid, 6-gingerol, eugenol and isohomogenol were potential active ingredients for RGHP's heat production effect. And UCP1, PGC-1α, PPARα and PPARγ are key thermogenesis proteins. CONCLUSIONS: RGHP treatment can significantly maintain the rectal temperature of mice by enhancing the BAT heat production. RGHP exhibited the heat production effect, which might be mainly attributed to increasing thermogenesis through the cAMP-PPAR signaling pathway in cold exposure mice. Oleic acid, 6-gingerol, eugenol and isohomogenol might be considered the potential therapeutic ingredients which affect the key targets of thermogenesis effect.

Adenosine 5'-monophosphate induces hypothermia and alters gene expressions in the brain and liver of chicks.

The adenosine A1 receptor is important for body temperature regulation in mammals; however, little is known about its function in avian species. In this study, we investigated the effects of the adenosine A1 receptor agonist and antagonist (adenosine 5'-monophosphate [5'-AMP] and 8 p-sulfophenyl theophylline [8-SPT], respectively) on thermoregulation in chickens. Male chicks were used in this study. After administration of 5'-AMP and 8-SPT, the rectal temperature, plasma metabolites, and gene expressions in the hypothalamus and liver were measured. The rectal temperature was reduced by peripheral administration of 5'-AMP, and the hypothermic effect of 5'-AMP was attenuated by central injection of 8-SPT in chicks. In the hypothalamus, the mRNA level of the agouti-related protein (AgRP) was increased by 5'-AMP administration, whereas it was suppressed by 8-SPT. The plasma levels of free fatty acid were elevated in 5'-AMP-treated chicks and that elevation was suppressed by the 8-SPT treatment. The gene expression of proopiomelanocortin in the hypothalamus was affected by 8-SPT. Nevertheless, the gene expressions of the thermoregulation-related genes, such as the thyrotropin-releasing hormone, were not affected by 5'-AMP and 8-SPT. Hepatic gene expressions related to lipid intake and metabolism were suppressed by 5'-AMP. However, the gene expression of the uncoupling protein was upregulated by 5'-AMP. Based on these results, birds, like mammals, will undergo adenosine A1 receptor-induced hypothermia. In conclusion, it is suggested that 5'-AMP-mediated hypothermia via the adenosine A1 receptor may affect the central melanocortin system and suppress hepatic lipid metabolism in chickens.

No thermoregulatory or ergogenic effect of dietary nitrate among physically inactive males, exercising above gas exchange threshold in hot and dry conditions.

The aim of this study was to determine the effect of five days dietary nitrate (NO3-) consumption on exercise tolerance and thermoregulation during cycling in hot, dry conditions. In a double-blind, randomised crossover design, 11 healthy males participated in an exercise tolerance test (Tlim) in the heat (35°C, 28% relative humidity), cycling above the thermoneutral gas exchange threshold, after five days of dietary supplementation, with either NO3-rich beetroot juice (BR; ∼ 9.2 mmol NO3-) or placebo (PLA). Changes in plasma [NO3-] and nitrite [NO2-], core and mean skin temperatures, mean local and whole-body sweat rates, heart rate, perceptual ratings and pulmonary gas exchange were measured during exercise, alongside calorimetric estimations of thermal balance. Mean arterial pressures (MAP) were recorded pre-Tlim. There were no differences in Tlim between conditions (BR = 22.8 ± 8.1 min; Placebo = 20.7 ± 7.9 min) (P = 0.184), despite increases in plasma [NO3-] and [NO2-] (P < 0.001) and a 3.8% reduction in resting MAP (P = 0.004) in the BR condition. There were no other differences in thermoregulatory, cardio-metabolic, perceptual or calorimetric responses to the Tlim between conditions (P > 0.05). Dietary NO3- supplementation had no effect on exercise tolerance or thermoregulation in hot, dry conditions, despite reductions in resting MAP and increases in plasma [NO3-] and [NO2-]. Healthy, yet physically inactive individuals with no known impairments in vasodilatory and sudomotor function do not appear to require BR for ergogenic or thermolytic effects during exercise in the heat.

The effects of melatonin daily supplementation to aged rats on the ability to withstand cold, thermoregulation and body weight.

AIMS: Investigate the role of melatonin on the regulation of body temperature in aged animals that have impaired melatonin production. MATERIAL AND METHODS: Aged Male Wistar rats were randomly assigned to the following groups: 1) control (vehicle added to the water bottles during the dark phase) and 2) melatonin-treated (10 mg/kg melatonin added to the water bottles during the dark phase). Before and after 16 weeks of vehicle or melatonin treatment, control group and melatonin-treated animals were acutely exposed to 18 °C for 2 h for an acute cold challenge and thermal images were obtained using an infrared camera. After 16 weeks, animals were euthanized and brown and beige adipocytes were collected for analysis of genes involved in the thermogenesis process by real-time PCR, and the uncoupling protein expression was evaluated by immunoblotting. Browning intensity of beige adipocytes were quantified by staining with hematoxylin-eosin. KEY FINDINGS: Chronic melatonin supplementation induced a minor increase in body mass and increased the animal's thermogenic potential in the cold acute challenge. Brown and beige adipocytes acted in a coordinated and complementary way to ensure adequate heat production. SIGNIFICANCE: Melatonin plays an important role in the thermoregulatory mechanisms, ensuring greater capacity to withstand cold and, also, participating in the regulation of energy balance.

Thermoregulatory, behavioral and productive responses of laying hens supplemented with different types and dosages of phytases raised in a hot environment: An integrative approach.

This study had the following objectives: (i) to evaluate the thermoregulatory and behavioral responses of light laying hens supplemented with different types and dosages of phytases in the two day shifts; and (ii) to integrate the thermoregulatory and behavioral responses with performance of these birds raised in a hot environment. 270 light laying hens of the Hy-Line White lineage, with a body weight of 1.60 ± 0.092 kg were distributed in a completely randomized design in a 2 × 2 + 1 factorial model with two types of phytases (bacterial and fungal) and two dosages (450 and 900 FTU), and a control diet. The day shift (morning and afternoon) was considered as a fixed effect in the factorial arrangement. Principal component analysis (PCA), correspondence analysis (CA) and canonical discriminant analysis (CDA) were used. There was no interaction (P > 0.05) between phytases and dosages for thermoregulatory responses. Respiratory rate (RR), cloacal temperature (CT), and surface temperature with feathers (STWF) and featherless (STF) were higher (P < 0.001) in the afternoon. Birds show different thermoregulatory and behavioral responses in the two shifts of the day. We also observed that birds supplemented with bacterial and fungal phytase showed similar thermoregulatory and behavioral responses to the control group in both day shifts. Expression of the "eating" activity was greater in the morning, while the birds remained sitting longer in the afternoon. Egg production was higher (P < 0.001) in birds supplemented with bacterial phytase. The phytase dosages had no effect on thermoregulatory, behavioral or performance responses. Egg production, feed conversion per dozen eggs corresponded to 81.1% of the differences between bacterial and fungal phytase supplementation and group control. Thus, we conclude that: (i) phytase dietary supplementation has no effect on the thermoregulatory responses of laying hens reared in a hot environment; (ii) birds supplemented with bacterial phytase showed higher egg production; and (iii) phytases (450 and 900 FTU) do not interfere with productive, behavioral and thermoregulatory responses.

Pharmacological evaluation of Acacia modesta bark for antipyretic, anti-inflammatory, analgesic, antidepressant and anticoagulant activities in Sprague Dawley rats.

In this study the bark of Acacia modesta was evaluated for anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activity by carrageenan, hot plat, forced swim and capillary tube method respectively in rats. Highest anti-inflammatory activity was exhibited by chloroform (AMC) extract (74.96% inhibition) while other two active fractions being n-hexane (AMH) and ethyl acetate (AME) exhibited 71.26% and 52.87% inhibition of edema respectively. On the other hand, the aqueous (AMA) fraction showed most effective response with 67.06% analgesic activity. Additionally, the significant (p<0.05) post-treatment antipyretic effect was found by all fractions in time dependent manner. The current findings showed that AMC, AME and AMA had significant reduction in immobility time in the antidepressant test, while AMH showed mild antidepressant activity. In anticoagulant assay, the coagulation time of crude extract A. modesta and its all fractions were comparable to that of positive control aspirin (208s). Moreover, neither mortality nor lethality was observed in the tested animals. Overall, the plant extracts showed potent anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activities which concludes that the bark of A. modesta have significant therapeutic potential.

Betaine Supplementation May Improve Heat Tolerance: Potential Mechanisms in Humans.

Betaine has been demonstrated to increase tolerance to hypertonic and thermal stressors. At the cellular level, intracellular betaine functions similar to molecular chaperones, thereby reducing the need for inducible heat shock protein expression. In addition to stabilizing protein conformations, betaine has been demonstrated to reduce oxidative damage. For the enterocyte, during periods of reduced perfusion as well as greater oxidative, thermal, and hypertonic stress (i.e., prolonged exercise in hot-humid conditions), betaine results in greater villi length and evidence for greater membrane integrity. Collectively, this reduces exercise-induced gut permeability, protecting against bacterial translocation and endotoxemia. At the systemic level, chronic betaine intake has been shown to reduce core temperature, all-cause mortality, markers of inflammation, and change blood chemistry in several animal models when exposed to heat stress. Despite convincing research in cell culture and animal models, only one published study exists exploring betaine's thermoregulatory function in humans. If the same premise holds true for humans, chronic betaine consumption may increase heat tolerance and provide another avenue of supplementation for those who find that heat stress is a major factor in their work, or training for exercise and sport. Yet, this remains speculative until data demonstrate such effects in humans.

Efeito da suplementação com óleo de avocado (Persea americana Mill) na temperatura superficial corpórea de equinos antes e após exercício em esteira / [Effect of supplementation with avocado oil (Persea americana Mill) on body surface temperature of horses before and after exercise on treadmill]

Oito equinos foram distribuídos em delineamento randomizado cruzado, sendo um grupo sem suplementação (GC) e outro grupo suplementado com óleo de avocado (GOAv) por um período de sete semanas. Ao fim da sexta semana, os animais foram submetidos a teste padrão de exercício progressivo (TPEP) e, após sete dias, a teste de baixa intensidade e longa duração (BILD). Após o primeiro ciclo, houve período de descanso "washout" de 30 dias para troca de grupos para o segundo ciclo, que seguiu o protocolo do primeiro. A termorregulação foi avaliada com base na temperatura retal e na temperatura superficial corpórea, obtidas por termografia, de 15 regiões de interesse. A temperatura retal e as imagens termográficas foram obtidas antes, um minuto e 15 minutos após o exercício. Não houve diferença entre os grupos GC e GOAv em nenhum momento. Os resultados obtidos neste estudo revelaram que a suplementação de 5% da matéria seca (MS) com óleo de avocado por seis e sete semanas não influenciou na termorregulação com base na temperatura superficial corpórea dos equinos submetidos ao teste padrão de exercício progressivo (TPEP) e ao exercício de baixa intensidade e longa duração (BILD), respectivamente.(AU)

Eight equines were distributed in a randomized crossover design, one control group (CG) without supplementation and another group supplemented (SG) with avocado oil for a period of six weeks. At the end of the sixth week, the animals were submitted to standard exercise test (SET) and after seven days to the low intensity test (LIT). After the first cycle, there was a 30-day washout rest period to exchange groups for the second cycle, which followed the protocol of the first one. Thermoregulation was evaluated based on rectal temperature and body surface temperature of 15 regions of interest obtained by thermography. Rectal temperature and thermographic images were obtained before, one minute and 15 minutes after exercise. There was no difference between the CG and SG at any time. The results obtained in this study revealed that the supplementation of 5% of dry matter with avocado oil for six and seven weeks did not influence the thermoregulation based on the body surface temperature of the horses submitted to SET and LIT, respectively.(AU)

Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.

NEW FINDINGS: What is the central question of this study? Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress? What is the main finding and its importance? A 7-day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post-supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat-stressed older individuals. ABSTRACT: This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole-body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7-day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 µmol l-1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole-body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment-by-time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.

Systemic acyl-ghrelin increases tail skin temperature in rats without affecting their thermoregulatory behavior in a cold environment.

Fasting increases ghrelin that is a peptide hormone with two circulating isoforms, acyl and des-acyl ghrelin. We reported that fasting or des-acyl ghrelin facilitates behavioral thermoregulation in the cold in rats assessed by tail-hiding behavior that was the indicator of rats' thermoregulatory behavior in the cold; however, the effect of acyl-ghrelin on the same process remains to be elucidated. We investigated the effect of acyl-ghrelin on thermoregulatory behavior in the cold in rats. The animals received an intraperitoneal saline or 24 µg acyl-ghrelin injection and were exposed to 27 °C or 15 °C for 2 h, while their body temperature, tail skin temperature, and tail-hiding behavior were constantly monitored. cFos immunoreactive (cFos-IR) cells in the median preoptic area, medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus were counted. Body temperature and the duration of thermoregulatory behavior did not show a significant difference between the acyl-ghrelin-treated and control groups at 15 °C; however, tail skin temperature in the acyl-ghrelin-treated group was higher than that in the control group. The number of cFos-IR cells in the PVN was greater in the control group than that in the acyl-ghrelin-treated group at 27 °C. These results indicate that acyl-ghrelin did not affect behavioral thermoregulation but might affect tail skin temperature in rats in the cold.

Pharmacological evaluation of analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of Indigofera argentea Burm. f.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera argentea Burm. f.; commonly known as neel, jantari, hathio; is traditionally used for the treatment of headache, fever, inflammation and body pain. Local communities also used this plant for the treatment of malaria, jaundice, vertigo and gastric disorders. AIM OF THE STUDY: This study is aimed to evaluate the toxicity and possible analgesic, anti-inflammatory and antipyretic activities of the ethanolic crude extract of Indigofera argentea (IaCr) to support its use in folk medicine and to screen the phytochemical constituents and antioxidant activity. MATERIALS AND METHODS: Aqueous ethanolic (30:70) extract of whole plant of Indigofera argentea (IaCr) was prepared and phytochemical study was performed by preliminary methods followed by HPLC and DPPH method. In vivo experiments were performed in Wistar albino rats including hot plate, tail immersion, formalin and capsaicin-induced pain tests in rats and acetic acid-induced writhing test in mice. Anti-inflammatory activity was assessed by using in vitro human red blood cell (HRBC) membrane stabilization and carrageenan-induced rat paw edema test, while antipyretic activity was evaluated by Brewer's yeast-induced pyrexia test. RESULTS: The crude extract of Indigofera argentea confirmed the presence of flavonoids, glycosides, alkaloids, saponins and tannins as soluble ethanolic constituents in preliminary study. The maximum quantity of gallic acid equivalent (GAE) phenolics, and quercetin equivalent (QE) flavonoid content found was 81 ± 2 mg GAE/g and 56 ± 1.4 mg QE/g of extract respectively. Quantification based on HPLC exposed the presence of phenols and flavonoids, quercetin, gallic acid, caffeic acid, chlorogenic acid, benzoic acid, ferulic acid and coumaric acid. In vivo experiments revealed significant P < 0.05) dose-dependent inhibition in hot plate, tail immersion and capsaicin-induced pain test. IaCr showed significant inhibition of pain latency against both phases in formalin test and considerably decreased the number of writhes caused by acetic acid at the doses of 30, 100 and 300 mg/kg. In the in vitro anti-inflammatory (HRBC) assay, IaCr showed good membrane stability with maximum percentage hemolysis inhibition of 49.29% while in carrageenan-induced paw edema test in rats the IaCr showed significant anti-inflammatory action in a dose-dependent fashion. Statistical significant reduction in rectal temperature was observed at the doses of 100 and 300 mg/kg in yeast-induced pyrexia test in rats. CONCLUSION: The results of the experimental studies proved the analgesic, anti-inflammatory and antipyretic activities of Indigofera argentea and supported the traditional use of this plant.

Does dietary supplementation with phytases affect the thermoregulatory and behavioral responses of pullets in a tropical environment?

Dietary supplementation of two types of phytases (fungal and bacterial) with different dosages (300 and 900 FTUs) was evaluated in the thermoregulatory and behavioral responses of replacement pullets in a tropical environment. 288 Hy-Line White laying birds with a mean weight of 639.60 ± 6.05 g, clinically healthy, and eight weeks old were used in the study. Respiratory rate (RR, breaths. min-1), Cloacal temperature (CT, °C), Surface temperature with feathers (STWF, °C), and Surface temperature featherless (STF, °C) were measured in the morning and afternoon. Behavioral data were observed through the following activities: sitting, eating, drinking, exploring feathers (EF), non-aggressive pecking (NAP), and object pecking (OP) recorded every 10 min from 6 a.m. to 5 p.m. Environmental variables were measured along with thermoregulatory and behavioral responses. There was an interaction for RR between phytase and period of the day (P < 0.05). The lowest RR (morning) was observed in fungal phytase. STF and STWF were higher (P < 0.05) in the afternoon. Birds supplemented with fungal phytase showed lower STWF (P < 0.05). The variables that contributed to explain physiological and behavioral responses are shown in order of importance for (i) periods of day: morning (sitting, STWF, drinking, eating, and CT) and afternoon (STF, STWF, OP, drinking, eating, RR and sitting); (ii) phytases: fungal (STF, STWF, RR, sitting, eating and drinking); and bacterial (RR, STF, STWF, CT and sitting). Thermoregulatory and behavioral responses were similar between dosages, but different between types of phytases. Birds supplemented with fungal phytase used sensible heat dissipation mechanisms and exhibited thermal comfort behaviors. The 300 and 900 FTUs phytase doses did not influence the thermoregulatory and behavioral responses of birds, while they showed natural heat dissipation and heat stress behaviors in the afternoon. We recommend a dietary supplementation of 300 FTUs fungal phytases.

Antimalarial activity of the aqueous extract of the latex of Aloe pirottae Berger. (Aloaceae) against Plasmodium berghei in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In spite of worldwide efforts, malaria remains one of the most devastating illnesses in the world. The huge number of lives it takes and the resistance of malaria parasites to current drugs necessitate the search for new effective antimalarial drugs. Medicinal plants have been the major source of such drugs and A. pirottae is one of these plants used traditionally for the treatment of malaria in Ethiopia. AIM: This study was aimed at evaluating the antimalarial activity of the aqueous extract of A. pirottae against chloroquine sensitive P. berghei in mice. MATERIALS AND METHODS: The extract was obtained by macerating the latex of A. pirottae with distilled water. To determine its antiplasmodial activity, a 4-day suppressive model was used by dividing 40 mice into five groups of 8 mice each and given 200, 400 & 600mg/kg of the extract, the standard drug (chloroquine 25mg/kg) and the vehicle (distilled water). Then parasite suppression by the extract, survival time and prevention of loss of body weight, rectal temperature and packed cell volume were assessed. All data were presented as the Mean ±â€¯SEM (Standard Error of the Mean) and analyzed using IBM SPSS version 20. RESULTS: The extract showed moderate antimalarial activity by significantly (p < 0.001) suppressing parasitemia at all dose levels with maximum parasitemia suppression of 47.0% and significantly (p < 0.01) increasing survival time. Furthermore, 400 mg/kg and 600 mg/kg doses showed significant (p < 0.01) prevention of loss in body weight, rectal temperature and packed cell volume. CONCLUSION: Based to the results of this study, A. pirottae is endowed with a moderate antimalarial activity that is in agreement with the traditional claim of A. pirottae, hence may be used as a basis for further studies to be conducted on antimalarial activity of the plant.

L-arginine supplementation during the final third of gestation improves litter uniformity and physical characteristics of neonatal piglet thermoregulation.

The study assessed the effects of dietary L-arginine supplementation from days 85 to 115 of gestation on sow performance, litter quality, piglet physiology and survival variables in the first 24 hr of life. Twenty multiparous sows, with a history of hyperprolificacy (more than 14 piglets per litter), were used. A completely randomized experimental design was used, consisting of two treatments: feed supplemented or not with 1% L-arginine from days 85 to 115 of gestation. The experimental unit consisted of the sow and its respective litter, using 10 replicates per treatment. The sows were distributed into the treatments based on body condition and parity. Supplementation with L-arginine reduced the within-litter standard deviation and the within-litter coefficient of variation of piglet weight at 24 hr by 54 g and 4.14 percentage points respectively (p = .029; p = .035). Supplementation with 1.0% L-arginine decreased the percentages of piglets weighing less than 800 g by 5.60 and 5.08 points at birth and at 24 hr of life respectively. Piglets from sows supplemented with L-arginine had higher (p = .088) average rectal temperatures at birth and lower (p = .030) rectal temperature at 24 hr of life in comparison with control piglets. No significant differences in placental weight or estimated colostrum production and intake were observed in the first 24 hr of life. At 24 hr of life, piglets weighing less than 1,000 g and from supplemented sows had lower (p = .048) surface/mass ratios and higher body mass index (p = .070). Piglets from supplemented sows and who weighed 1601 to 1,800 g had lower body mass index and ponderal index (p = .002; p = .003). Supplementation with L-arginine during the final third of gestation reduces the incidence of unviable piglets (<800 g) and improved litter uniformity and piglets' body conformation within the first 24 hr of life.

Oral L-Tyrosine Supplementation Improves Core Temperature Maintenance in Older Adults.

INTRODUCTION: During cold exposure, an increase in sympathetic nerve activity evokes vasoconstriction (VC) of cutaneous vessels to minimize heat loss. In older adults, this reflex VC response is impaired thereby increasing their susceptibility to excess heat loss and hypothermia. Because L-tyrosine, the amino acid substrate necessary for catecholamine production, has been shown to augment reflex VC in age skin, we hypothesize that oral ingestion of L-tyrosine will attenuate the decline in core temperature (Tc) during whole-body cooling in older adults. METHODS: In a randomized, double-blind design, nine young (25 ± 3 yr) and nine older (72 ± 8 yr) participants ingested either 150 mg·kg of L-tyrosine or placebo before commencing 90 min of whole-body cooling to decrease skin temperature to approximately 29.5°C. Esophageal temperature and forearm laser Doppler flux (LDF) were measured continuously throughout the protocol to provide an index of Tc and skin blood flow, respectively. The change in esophageal temperature (ΔTES) was the difference in temperature at the end of cooling subtracted from baseline. Cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVCBASELINE). RESULTS: Oral tyrosine ingestion augmented the cutaneous VC response to cooling in older adults (placebo, 14.4 ± 2.0; tyrosine, 32.7% ± 1.7% ΔCVCBASELINE; P < 0.05). Additionally, tyrosine improved Tc maintenance throughout cooling in older adults (placebo, -0.29 ± 0.07; tyrosine, -0.07 ± 0.07 ΔTES; P < 0.05). Both the cutaneous VC and Tc during cooling were similar between young and older adults supplemented with tyrosine (P > 0.05). CONCLUSIONS: These results indicate that L-tyrosine supplementation improves Tc maintenance in response to acute cold exposure in an older population.

The Chinese medicinal herbs of spleen-meridian property regulate body temperature in yeast-induced fever rats.

BACKGROUND: According to traditional Chinese medicine (TCM) theory, the herbal property is the most important guiding principle of ancient medication in China. The classification of warm- and cold-stimulating TCM is defined mainly based on the effects of herbs in regulating body temperature; however, the underlying mechanism of such distinction has not been fully identified. METHODS: Here, four commonly used spleen-meridian herbs, Ginseng Radix and Astragali Radix as typical warm-stimulating herbs, and Nelumbinis Semen and Coicis Semen as typical cold-stimulating herbs, were selected to test their effects in regulating body temperature, as well as its triggered thermo-regulatory factors and energy related metabolites, in yeast-induced fever rats. RESULTS: The intake of Astragali Radix increased body temperature in yeast-induced fever rats; while Coicis Semen showed cooling effects in such rats. In parallel, the levels of cAMP, PGE2 and thermo-related metabolites, including choline, creatine, alanine, lactate and leucine, in the blood of yeast-induced rats were increased significantly by the intake of Astragali Radix. Oppositely, the cold-stimulating herbs, Nelumbinis Semen and Coicis Semen, showed cooling effects by increasing certain metabolites, e.g. histidine, tyrosine, lipid, myo-inositol, as well as AVP level. CONCLUSION: Here, we compared different effects of warm and cooling spleen-meridian herbs in the regulation of body temperature. By providing an intuitive comparison of thermo-regulatory factors and related metabolites after intake of selected herbs, the mechanism behind the warm and cooling effects of specific herbs were revealed.