5-Hydroxytryptophan: A precursor of serotonin influences regional blood-brain barrier breakdown, cerebral blood flow, brain edema formation, and neuropathology

Sharma, Aruna; Castellani, Rudy J.; Smith, Mark A.; Mureșanu, Dafin F.; Dey, Prasanta Kumar; Sharma, Hari Shanker

doi:10.1016/bs.irn.2019.06.005

Cited by 37 publications

(15 citation statements)

References 111 publications

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“…The mRNA expression of gene encoding 5-HT2A in both liver and abdominal fat was consistent with the finding of unaffected circulating levels of 5-HT. In rats, however, the endogenous serotonin levels increased in the plasma and brain at 4 h after 5-HTP administrations (Sharma et al, 2019).…”

Section: -Htp Reduces Abdominal Fat Accumulationmentioning

confidence: 88%

5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers

Wang

Liu

et al. 2020

Front. Physiol.

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Background: Serotonin (5-HT), a monoaminergic neurotransmitter, involves in the regulation of many physiological functions. In the present study, the effects of 5hydroxytryptophan (5-HTP), the precursor of 5-HT, on lipid metabolism and intestinal immune function in broiler chickens were investigated in chickens. Methods: Two hundred broilers were divided randomly into two groups and fed separately with a corn-soybean basal diet (CD) or the basal diet supplemented with 0.2% 5-HTP. Results: The results showed that 5-HTP reduced (P < 0.05) feed intake and the abdominal fat pad weight. 5-HTP treatment tended to upregulate the mRNA level of adiponectin receptor 1 (ADP1R) and ADP2R in abdominal fat but had no significant influence on their protein levels (P > 0.05). In 5-HTP-chickens, lipopolysaccharide exposure decreased secretory immunoglobulin A (sIgA) concentrations in serum and the duodenal contents. Expression of mRNA encoding interleukin (IL), tumor necrosis factorα (TNF-α), and transforming growth factor-β (TGF-β) decreased after 5-HTP treatment; however, LPS increased expression significantly in 5-HTP-treated chickens compared with CD chickens. In 5-HTP-chickens, the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were reduced, but the phosphorylation of ribosomal p70S6 kinase (p70S6K) was increased in the duodenum. Conclusion: In summary, the result suggests that dietary 5-HTP supplementation reduces accumulation of abdominal fat and is beneficial to intestinal immune function.

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Section: -Htp Reduces Abdominal Fat Accumulationmentioning

confidence: 88%

5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers

Wang

Liu

et al. 2020

Front. Physiol.

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“…The extent to which serotonin crosses the blood-brain barrier is controversial. 16,22,23,53,[65][66][67] In this study, we did not have the opportunity to measure serotonin in the CNS or in adipocytes in individuals with FA. It is possible that CNS serotonin, and production and metabolism of serotonin in tissues such as adipocytes, is also abnormal in FA, contributing to metabolic and phenotypic changes in individuals with FA.…”

Section: Discussionmentioning

confidence: 99%

Tryptophan metabolism is dysregulated in individuals with Fanconi anemia

et al. 2021

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Fanconi anemia (FA) is a complex genetic disorder associated with progressive marrow failure and a strong predisposition to malignancy. FA is associated with metabolic disturbances such as short stature, insulin resistance, thyroid dysfunction, abnormal body mass index (BMI), and dyslipidemia. We studied tryptophan metabolism in FA by examining tryptophan and its metabolites before and during the stress of hematopoietic stem cell transplant (HSCT). Tryptophan is an essential amino acid that can be converted to serotonin and kynurenine. We report here that serotonin levels are markedly elevated 14 days after HSCT in individuals with FA, in contrast to individuals without FA. Kynurenine levels are significantly reduced in individuals with FA compared with individuals without FA, before and after HSCT. Most peripheral serotonin is made in the bowel. However, serotonin levels in stool decreased in individuals with FA after transplant, similar to individuals without FA. Instead, we detected serotonin production in the skin in individuals with FA, whereas none was seen in individuals without FA. As expected, serotonin and transforming growth factor β (TGF-β) levels were closely correlated with platelet count before and after HSCT in persons without FA. In FA, neither baseline serotonin nor TGF-B correlated with baseline platelet count (host-derived platelets), only TGF-B correlated 14 days after transplant (blood bank-derived platelets). BMI was negatively correlated with serotonin in individuals with FA, suggesting that hyperserotonemia may contribute to growth failure in FA. Serotonin is a potential therapeutic target, and currently available drugs might be beneficial in restoring metabolic balance in individuals with FA.

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“…In rats, at least some of the behavioral effects of 5-HTP are due to increased levels or turnover of 5-HTP in peripheral serotonergic neuronal systems [ 105 ] and 5-HTP neurotoxicity caused by brain–blood barrier breakdown, edema formation, and NO production was found to be instrumental in causing adverse mental and behavioral abnormalities [ 106 ]. For instance, the wet dog shake behavior induced by 5-HTP was dose dependent and was mediated by the activation of 5-HT2 receptors [ 107 ], whereas in iproniazid-pretreated rats, a special form of stereotyped movements of the head and forelegs and a gnawing behavior were observed after intraperitoneal administration of 5-HTP [ 108 ].…”

Section: Physiological Effects Of 5-htpmentioning

confidence: 99%

“…Clinically relevant ingestion of 5-HTP in dogs was found to result in a potentially life-threatening syndrome resembling serotonin syndrome in humans, which requires prompt and aggressive care [ 188 ]. After 5-HTP administration, the endogenous serotonin levels increased by fourfold in the rat plasma and brain, associated with profound hyperthermia, oxidative stress, and NO upregulation [ 106 ].…”

Section: Toxicology Of 5-htpmentioning

confidence: 99%

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

Maffei

2020

IJMS

118

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L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.

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5-Hydroxytryptophan: A precursor of serotonin influences regional blood-brain barrier breakdown, cerebral blood flow, brain edema formation, and neuropathology

Cited by 37 publications

References 111 publications

5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers

5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers

Tryptophan metabolism is dysregulated in individuals with Fanconi anemia

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

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