# Effects of _Aloe vera_ on the Regulation of Thyroxine Release in FRTL-5 Thyroid Cells
###### Abstract  
To determine whether _Aloe vera_ (AV), a traditional herbal medicine, could maintain homeostasis, we investigated its ability to regulate the production of hormones, particularly thyroid hormones. T4 ELISA assay with (6H media) and without thyrotropin (TSH) (5H media) showed that AV functions to maintain endocrine homeostasis. To understand the mechanisms by which AV regulates thyroxine release, we confirmed the protein expression of key upstream factors of thyroid hormone synthesis, such as phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated cAMP response element binding protein (CREB), and phosphorylated protein kinase B (p-Akt). Although the protein expression of phosphorylated ERK and CREB were decreased in 6H media, they were increased and unchanged, respectively, in 5H media. However, protein expression of phosphorylated Akt was not changed by AV in both 6H and 5H media. Furthermore, inhibition of protein kinase A (PKA) by H89 eliminated AV-induced phosphorylation of ERK in 5H media. However, the inhibition of protein kinase C (PKC) by GF 109203X did not eliminate AV-induced ERK phosphorylation in 5H media. These results suggested that AV has TSH-like activity and could regulate thyroxine release through the TPO and PKA pathways. AV may regulate thyroid function to maintain a constant level of thyroid hormones in the body, and could be a candidate for thyroid disease therapies.  
Aloe vera(AV); FRTL-5 cells; homeostasis; thyroid hormones +
Footnote †: journal: Medical  
demonstrated using meta-analysis [3]. Effects of Chinese herbal formulas and herb-derived bioactive compounds on allergic asthma caused by an imbalance of immune regulation have been proven in several experimental models [4]. The Fuzi-Lizhong pill increased ghrelin release and improved chronic hypothermia in rats with hypothyroidism and indigestion [5]. However, there have been no reports on whether herbal medicines regulate the feedback system of thyroid hormones.  
In this study, we found that _Aloe vera_ (AV), a traditional herbal medicine, regulates the feedback system of thyroid hormones in FRTL-5 thyroid cells. In [PERSON]'s illustrated guide medicinal materials, _Aloe vera_ Linne (_A. barbadensis_ [PERSON], _A. frox_ [PERSON], _A. africana_ [PERSON], and _A. spicata_ [PERSON]), known as Nohoe, belonged to the family Liliaceae that originated in Republic of Korea, China, and South Africa [6]. Of the herbs of the Tangaek section of Donguibogam, a Korean medical book, it was first mentioned and was known to contain several bioactive components, such as vitamins, minerals, sugars, and enzymes [7]. Due to these components, AV has several nutritional and therapeutic properties and beneficial effects, including anti-inflammatory, anti-oxidative, anti-bacterial effects, and regulation of intestinal function, have been widely reported. Therefore, it is used to treat constipation, skin disease, infections, diabetes, and gastrointestinal disorders, among several other diseases [8; 9; 10; 11]. For example, AV metabolites exhibit anti-inflammatory effects by reducing the production of pro-inflammatory cytokines in lipopolysaccharide-induced septic mice, LPS-activated RAW264.7 macrophages, and murine peritoneal macrophages [12]. AV extract showed protective effects on pancreatic islets by restoring pancreatic islet mass and improving diabetes in rats with streptozotocinocin (STZ)-induced diabetes [13].  
This study aimed to evaluate the ability of AV to maintain homeostasis, similar to TSH. We examined the role of AV in regulating the cellular export of thyroid hormones, and its cellular mechanism in FRTL-5 thyroid cells.