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      Ephedra sinica Stapf and Gypsum Attenuates Heat-Induced Hypothalamic Inflammation in Mice

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          Abstract

          Ephedra sinica Stapf (EH) exert toxic effects, such as excitability, cardiac arrhythmia, and others. On the contrary, in traditional herbal medicine, EH and gypsum (GF) are used most often to treat symptoms caused by external stressors. The hypothalamus plays a crucial role in thermal homeostasis. Inflammatory response in the hypothalamus by thermal stressors may affect thermal and energy homeostasis. This study investigates the effect of EH and GF against heat-induced mouse model. Mice were divided into four groups: saline, saline plus heat, EH plus heat, and GF plus heat treated groups. Heat stress was fixed at 43 °C for 15 min once daily for 3 days. Weight and ear and rectal temperature measurements were made after terminating heat stress. Hypothalamus tissue was collected to evaluate the HSP70, nuclear factor kappa-Β (NF-kB), and interleukin (IL)-1β protein expression levels. EH and GF treatment suppressed the increased body temperature. EH significantly ameliorated heat-induced body weight loss, compared to gypsum. Regulatory effects of EH and GF for body temperature and weight against heat stress were mediated by IL-1β reduction. EH showed significant HSP70 and NF-kB inhibition against heat stress. EH and GF contribute to the inhibition of heat-induced proinflammatory factors and the promotion of hypothalamic homeostasis.

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          Most cited references23

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          Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system.

          While summarizing the current understanding of how body temperature (T(b)) is regulated, this review discusses the recent progress in the following areas: central and peripheral thermosensitivity and temperature-activated transient receptor potential (TRP) channels; afferent neuronal pathways from peripheral thermosensors; and efferent thermoeffector pathways. It is proposed that activation of temperature-sensitive TRP channels is a mechanism of peripheral thermosensitivity. Special attention is paid to the functional architecture of the thermoregulatory system. The notion that deep T(b) is regulated by a unified system with a single controller is rejected. It is proposed that T(b) is regulated by independent thermoeffector loops, each having its own afferent and efferent branches. The activity of each thermoeffector is triggered by a unique combination of shell and core T(b)s. Temperature-dependent phase transitions in thermosensory neurons cause sequential activation of all neurons of the corresponding thermoeffector loop and eventually a thermoeffector response. No computation of an integrated T(b) or its comparison with an obvious or hidden set point of a unified system is necessary. Coordination between thermoeffectors is achieved through their common controlled variable, T(b). The described model incorporates Kobayashi's views, but Kobayashi's proposal to eliminate the term sensor is rejected. A case against the term set point is also made. Because this term is historically associated with a unified control system, it is more misleading than informative. The term balance point is proposed to designate the regulated level of T(b) and to attract attention to the multiple feedback, feedforward, and open-loop components that contribute to thermal balance.
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            Recent advances in thermoregulation.

            Thermoregulation is the maintenance of a relatively constant core body temperature. Humans normally maintain a body temperature at 37°C, and maintenance of this relatively high temperature is critical to human survival. This concept is so important that control of thermoregulation is often the principal example cited when teaching physiological homeostasis. A basic understanding of the processes underpinning temperature regulation is necessary for all undergraduate students studying biology and biology-related disciplines, and a thorough understanding is necessary for those students in clinical training. Our aim in this review is to broadly present the thermoregulatory process taking into account current advances in this area. First, we summarize the basic concepts of thermoregulation and subsequently assess the physiological responses to heat and cold stress, including vasodilation and vasoconstriction, sweating, nonshivering thermogenesis, piloerection, shivering, and altered behavior. Current research is presented concerning the body's detection of thermal challenge, peripheral and central thermoregulatory control mechanisms, including brown adipose tissue in adult humans and temperature transduction by the relatively recently discovered transient receptor potential channels. Finally, we present an updated understanding of the neuroanatomic circuitry supporting thermoregulation.
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              Hypothalamic inflammation: a double-edged sword to nutritional diseases.

              The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and nonneuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases. Recent research has begun to elucidate the effects of hypothalamic inflammation in causing diverse components of metabolic syndrome leading to diabetes and cardiovascular disease. These new understandings have provocatively expanded previous knowledge on the cachectic roles of brain inflammatory response in diseases, such as infections and cancers. This review describes the molecular and cellular characteristics of hypothalamic inflammation in metabolic syndrome and related diseases as opposed to cachectic diseases, and also discusses concepts and potential applications of inhibiting central/hypothalamic inflammation to treat nutritional diseases. © 2012 New York Academy of Sciences.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                30 December 2019
                January 2020
                : 12
                : 1
                : 16
                Affiliations
                [1 ]Division of Pharmacology, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon 27136, Korea
                [2 ]Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
                [3 ]Department of Medical Science of Meridian, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
                [4 ]Department of Oriental Pharmaceutical Science, College of Pharmacy Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
                [5 ]Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan 54538, Korea
                [6 ]Department of Formulae Pharmacology, School of Oriental Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 13120, Korea
                [7 ]Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
                Author notes
                [* ]Correspondence: msohok@ 123456khu.ac.kr ; Tel.: +82-2-961-9436
                Author information
                https://orcid.org/0000-0001-6169-0402
                Article
                toxins-12-00016
                10.3390/toxins12010016
                7020418
                31905825
                e267d325-38b7-45e7-90d6-8b2af9c950c5
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 November 2019
                : 27 December 2019
                Categories
                Communication

                Molecular medicine
                ephedra sinica stapf,gypsum,heat stress,hypothalamus,inflammation
                Molecular medicine
                ephedra sinica stapf, gypsum, heat stress, hypothalamus, inflammation

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