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User:Mollynikita/sandbox

Mollynikita/sandbox
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administration		Oral
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  • Over-the-counter
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  • (1R,5S,6R,7S)-4-Hydroxy-6-methyl-5-(2-methylbutanoyl)-1,3,7-tris(3-methyl-2-buten-1-yl)-6-(4-methyl-3-penten-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione
CAS Number
PubChem CID
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Chemical and physical data
FormulaC36H54O4
Molar mass550.81156 g/mol g·mol−1
3D model (JSmol)
  • CCC(C)C(=O)C12C(=C(C(=O)C(C1=O)(CC(C2(C)CCC=C(C)C)CC=C(C)C)CC=C(C)C)CC=C(C)C)O
  • InChI=1S/C36H54O4/c1-12-27(10)30(37)36-32(39)29(18-16-25(6)7)31(38)35(33(36)40,21-19-26(8)9)22-28(17-15-24(4)5)34(36,11)20-13-14-23(2)3/h14-16,19,27-28,39H,12-13,17-18,20-22H2,1-11H3/t27?,28-,34+,35+,36-/m0/s1 ☒N
  • Key:DHPDSOCOUJHGHE-ACJQSPJVSA-N ☒N
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Adhyperforin is a phytochemical that is a member of the plant genus Hypericum, which includes plants such as St. John's Wort.[1] It has a very similar pharmacological profile to hyperforin and acts as a TRPC6 ion channel activator,[1] meaning it inhibits the reuptake of neurotransmitters such as serotonin, norepinephrine, dopamine, GABA, and glutamate.[1]

A phloroglucinol derivative of H. perforatum, adhyperforin is primarily used as an antidepressant. It is part of the lipophilic extract of St. John's Wort, and demonstrates a variety of therapeutic effects, including treatment of wounds, burns, cuts, hemorrhoids, gastric spasms, insomnia, and muscular pain.[2][3][4]

Chemical Properties edit

Adhyperforin is soluble in methanol and ethanol. When fully dissolved, it produces a slightly colored solution. Like other hyperforins, adhyperforin is extremely unstable, particularly when solid. Solid adhyperforin will break down rapidly when exposed to oxygen and light.[5] Its complete degradation process takes approximately 25 minutes.[4]

Compound History edit

While St. John's Wort is known for its antidepressive properties, hyperforin was conventionally assumed to be the factor responsible for its therapeutic effects. A number of studies used hyperforin-enriched lipophilic extracts to demonstrate hyperforin's role in decreasing neurotransmitter reuptake.[6][7] In 2003, experiments using St. John's Wort with hyperforin and hypericin extracts revealed that neither were necessary to produce St. John's Wort's antidepressive effects. Following this discovery, the role of adhyperforin in St. John's Wort has been increasingly investigated.[8]

Pharmacodynamics edit

Adhyperforin is more potent than hyperforin, another phloroglucinol derivative of H. perforatum.[1] Both compounds are among the primary active ingredients of St. John’s Wort, but other derivatives found in the lipophilic portion of the plant are also necessary for St. John's Wort to be able to exert its full effect.[1]

Although the binding site for adhyperforin on the TRPC6 ion channel is still unknown, binding of adhyperforin to its receptor results in similar antidepressive effects to those of selective serontonin reuptake inhibitors and norepinephrine reuptake inhibitors. Adhyperforin has been shown to inhibit the reuptake of serotonin, norepinephrine, dopamine, and choline neurotransmitters when administered at potencies comparable to those of existing drugs. [3] [1] While adhyperforin demonstrates high binding affinities for NET and SERT, the exact mechanism for the inhibitory activity of adhyperforin on dopamine reuptake remains unclear. Further investigation is needed to determine the components of this pathway.[9]

Adhyperforin also inhibits reuptake of GABA and glutamate via activation of TRPC6. Additionally, adhyperforin activates the pregnane X receptor.[5] As a triple-reuptake inhibitor, adhyperforin is able to increase the amount of monoamines in the synaptic cleft.[9]

Pharmacokinetics edit

Pharmacokinetic study of isolated adhyperforin remains to be conducted in humans.

In mouse models, adhyperforin has an ID50 value of 0.30mmol cm-2.[10] Adhyperforin also exhibits strong binding affinities to SERT (Ki=18.75±7.76 μg/ml) and NET (Ki=4.03±0.37 μg/ml). [9]

Treatment edit

St. John’s Wort has historically been used in traditional healing practices. The lipophilic extract of St. John's Wort, which primarily contains adhyperforin and hyperforin as active ingredients, is often used by traditional healers to act as an antimicrobial or anti-inflammatory agent.[4] In modern allopathic medicine, adhyperforin and hyperforin contribute to St. John's Wort's antidepressive effects, as well.[4] While the medicinal properties of St. John's Wort are well understood in humans, the effects of adhyperforin alone have not been extensively studied.

The effects of adhyperforin administration have been briefly explored in animal models, particularly in rats. Rat models support adhyperforin as a potential antidepressant.[9] Behavioral testing assays conducted with rats have illustrated that treatment with adhyperforin successfully antagonized the effects of reserpine. When administered to a rat model for chronic unpredictable mild stress, adhyperforin significantly improved rats’ anhedonia and hypoactivity, further demonstrating antidepressant-like properties. [9]

In mouse models, solutions containing both adhyperforin and hyperforin inhibit edema. The application of the oily extract of St. John’s Wort, which contains hyperforin and adhyperforin, has also been shown to reduce ear inflammation in rats. This suggests that adhyperforin may perform an antiphlogistic role in the body.

As St. John's Wort continues to be a widely administered herbal oral and topical medication, adhyperforin is also widely, albeit perhaps unknowingly, used.

Side Effects edit

At this point, little is known about what adhyperforin's potential side effects would be if administered as an antidepressant alone--further research and clinical trials still need to be conducted. It is believed, however, that H. perforatum extracts such as adhyperforin may have an advantage over drugs that are traditionally associated with the treatment of depression, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, because the H. perforatum extracts may have fewer side effects and be cheaper than the available alternatives.[9]

Synthesis/Derivation edit

Adhyperforin is traditionally isolated from the generative parts of St. John’s Wort plants, particularly from their unripe fruit and flowering parts. [10]Plant material collected when fruits are developing or at the end of their flowering periods yields greater amounts of adhyperforin product than does derivation from fruits during the middle of the flowering season.[3] Regardless of the time at which a sample is obtained, isolation of adhyperforin typically yields ten times less product than does isolation of hyperforin. This ratio depends upon plant processing time, plant locale, and plant environment.[1]

The process itself used to isolate adhyperforin from St. John’s Wort is similar to the isolation method used for hyperforin.[3]

Newer synthesis and isolation methods involve the use of Accelerated Solvent Extraction (ASE) coupled with High-Performance Counter-Current Chromatography (HPCCC) technology. Such methods are promising as they reduce the time necessary for collection, retain a higher adhyperforin purity, and yield high levels of all phloroglucinol extracts. [11]

Other methods utilize supercritical fluid extraction (SFE) with carbon dioxide to isolate all lipophilic compounds from St. John's Wort. SFE is comparable to ultrasonic or boiling methods of isolation in terms of yield of adhyperforin produced.[12]

In order to enhance adhyperforin production, exogenous L-isoleucine and L-threonine is added to shoot cultures.[13] Not all amino acid supplementation causes enhanced production of adhyperforin; for example, the addition of L-valine and L-leucine to root extracts of St. John's Wort does not result in greater yields of adhyperforin.[13]

While the biosynthesis of adhyperforin is often studied in H. perforatum cells, H. calycinum cells are also a useful system for evaluating adhyperforin activity. Because adhyperforin is derived from methylbutyryl-CoA, which is present in higher levels in H. calycinum cells than in H. perforatum, higher yields of adhyperforin are produced from H.calycinum cells.[14] Quantitatively, as in H.perforatum cells, in H. calycinum cell cultures, adhyperforin is produced at ten times the level of hyperforin produced.[14]

See also edit

References edit

  1. ^ a b c d e f g Jensen AG, Hansen SH, Nielsen EO. (2001). "Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity". Life Sci. 68 (14): 1593–1605. doi:10.1016/S0024-3205(01)00946-8. PMID 11263672.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Gurhan, Gul; Ezer, Nyal. "The plants used in the treatment of hemorrhoid by local people". Journal of Pharmacy Faculty of Hacettepe University. 24: 37-55.
  3. ^ a b c d Butterweck, Veronika; Schmidt, Mathias (2007). "St. John's Wort: Role of Active Compounds for Its Mechanism of Action and Efficacy". Wiener Medizinische Wochenschrift. 157 (13–14): 356–61. doi:10.1007/s10354-007-0440-8. PMID 17704987. S2CID 19259132.
  4. ^ a b c d Kirakosyan, A; Sirvent, TM; Gibson, DM; Kaufman, PB (February 2004). "The production of hypericins and hyperforin by in vitro cultures of St. John's wort (Hypericum perforatum)". Biotechnology and Applied Biochemistry. 39 (Pt 1): 71–81. doi:10.1042/BA20030144. PMID 14521510. S2CID 30445763.
  5. ^ a b "Adhyperforin". Kerafast.
  6. ^ Bhattacharya, SK; Chakrabarti, A; Chatterjee, SS (June 1998). "Activity profiles of two hyperforin-containing hypericum extracts in behavioral models". Pharmacopsychiatry. 31 Suppl 1: 22–9. doi:10.1055/s-2007-979342. PMID 9684944.
  7. ^ Chatterjee, SS; Nöldner, M; Koch, E; Erdelmeier, C (June 1998). "Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility". Pharmacopsychiatry. 31 Suppl 1: 7–15. doi:10.1055/s-2007-979340. PMID 9684942.
  8. ^ Butterweck, Veronika; Christoffel, Volker; Nahrstedt, Adolf; Petereit, Frank; Spengler, Barbara; Winterhoff, Hilke (June 2003). "Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models". Life Sciences. 73 (5): 627–639. doi:10.1016/S0024-3205(03)00314-X. PMID 12770617.
  9. ^ a b c d e f Tian, Jingwei; Zhang, Fangxi; Cheng, Jucan; Guo, Shuren; Liu, Pinglan; Wang, Hongbo (9 July 2014). "Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L.". Scientific Reports. 4. doi:10.1038/srep05632. PMID 25005489. S2CID 14632973.
  10. ^ a b Sosa, S; Pace, R; Bornancin, A; Morazzoni, P; Riva, A; Tubaro, A; Della Loggia, R (May 2007). "Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L.". The Journal of Pharmacy and Pharmacology. 59 (5): 703–9. doi:10.1211/jpp.59.5.0011. PMID 17524236. S2CID 24954384.
  11. ^ Zhang, Yuchi; Chunming, Liu; Yu, Min; Zhang, Zhengkum; Qi, Yanjuan; Wang, Jing; Wu, Guimei; Li, Sianan; Yu, Jing; Hu, Yang (May 20, 2011). "Application of Accelerated Solvent Extraction Coupled with High-Performance Counter-Current Chromatography to Extraction and Online Isolation of Chemical Constituents from Hypericum Perforatum L.". Journal of Chromatography. 1218 (20): 2827–34. doi:10.1016/j.chroma.2011.03.007. PMID 21439573.
  12. ^ Mannila, Mari; Kim, Hakwon; Isaacson, Carl; Wai, Chien M. (8 August 2002). "Optimization of supercritical fluid extraction for the separation of hyperforin and adhyperforin in St. John???s wort (Hypericum perforatum L.)". Green Chemistry. 4 (4): 331–336. doi:10.1039/B201363K.
  13. ^ a b Karppinen, K; Hokkanen, J; Tolonen, A; Mattila, S; Hohtola, A (April 2007). "Biosynthesis of hyperforin and adhyperforin from amino acid precursors in shoot cultures of Hypericum perforatum". Phytochemistry. 68 (7): 1038–45. doi:10.1016/j.phytochem.2007.01.001. PMID 17307206.
  14. ^ a b Klingauf, P; Beuerle, T; Mellenthin, A; El-Moghazy, SA; Boubakir, Z; Beerhues, L (January 2005). "Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures". Phytochemistry. 66 (2): 139–45. doi:10.1016/j.phytochem.2004.11.003. PMID 15652570.

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