Monday, 3 July 2017

Dihydroartemisinin kháng Bel-7402

[HTML] Dihydroartemisinin-induced inhibition of proliferation in BEL-7402 cells: An analysis of the mitochondrial proteome

Dihydroartemisinin kháng Bel-7402

From Wikipedia, the free encyclopedia
Dihydroartemisinin
Artenimol.png
Dihydroartemisinin 3D balls.png
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability12%
MetabolismLiver
Biological half-lifeAbout 4–11 hours
ExcretionMainly Bile
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
ECHA InfoCard100.128.242
Chemical and physical data
FormulaC15H24O5
Molar mass284.35 g/mol
3D model (Jmol)
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Dihydroartemisinin (also known as dihydroqinghaosu, artenimol or DHA) is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs.[1] It is sold commercially in combination with piperaquineand has been shown to be equivalent to artemether/lumefantrine.[2]

Medical use[edit]

Dihydroartemisinin is used to treat malaria, generally as a combination drug with piperaquine.[3]
In a systematic review of randomized controlled trials, both dihydroartemisinin-piperaquine and artemether-lumefantrine are very effective at treating malaria (high quality evidence). However, dihydroartemisinin-piperaquine cures slightly more patients than artemether-lumefantrine, and it also prevents further malaria infections for longer after treatment (high quality evidence). Dihydroartemisinin-piperaquine and artemether-lumefantrine probably have similar side effects (moderate quality evidence). The studies were all conducted in Africa. In studies of people living in Asia, dihydroartemisinin-piperaquine is as effective as artesunate plus mefloquine at treating malaria (moderate quality evidence). Artesunate plus mefloquine probably causes more nausea, vomiting, dizziness, sleeplessness, and palpitations than dihydroartemisinin-piperaquine (moderate quality evidence).[4]

Pharmacology and mechanism[edit]

Seeds
The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) which damage biological macromolecules causing oxidative stress in the cells of the parasite.[5] Malaria is caused by apicomplexans, primarily Plasmodium falciparum, which largely reside in red blood cells and itself contains iron-rich heme-groups (in the form of hemozoin).[6] In 2015 artemisinin was shown to bind to a large number targets suggesting that it acts in a promiscuous manner.[7]Recent mechanism research discovered that artemisinin targets a broad spectrum of proteins in the human cancer cell proteome through heme-activated radical alkylation. [8]

Chemistry[edit]

Dihydroartemisinin has a low solubility in water of less than 0.1 g/L. Consequently, its use may results in side effects caused by minor, yet much more soluble, additives (excipients) such as Cremophor EL.[9]
The lactone of artemisinin could selectively be reduced with mild hydride-reducing agents, such as sodium borohydride, potassium borohydride, and lithium borohydride to dihydroartemisinin (a lactol) in over 90% yield. It is a novel reduction, because normally lactone cannot be reduced with sodium borohydride under the same reaction conditions (0–5 ˚C in methanol). Reduction with LiAlH4 leads to some rearranged products. It was surprising to find that the lactone was reduced, but that the peroxy group survived. However, the lactone of deoxyartemisinin resisted reduction with sodium borohydride and could only be reduced with diisobutylaluminium hydride to the lactol deoxydihydroartimisinin. These results show that the peroxy group assists the reduction of lactone with sodium borohydride to a lactol, but not to the alcohol which is the over-reduction product. No clear evidence for this reduction process exists.[citation needed]

Society and culture[edit]

In combination with piperaquine, brands include:[citation needed]
  • D-Artepp (GPSC)
  • Artekin (Holleykin)
  • Diphos ( Genix Pharma)
  • TimeQuin ( Sami Pharma )
  • Eurartesim (Sigma Tau; by Good Manufacturing Practices)
  • Duocotecxin (Holley Pharm)
Alone (not recommended by WHO due to risk of resistance development):[citation needed]
  • Cotecxin (Zhejiang Holley Nanhu Pharmaceutical Co.)

Research[edit]

Accumulative research suggests that dihydroartemisinin and other artemisinin-based endoperoxide compounds may display activity as experimental cancer chemotherapeutics.[10] Recent pharmacological evidence demonstrates that dihydroartemisinin targets human metastatic melanoma cells with induction of NOXA-dependent mitochondrial apoptosis that occurs downstream of iron-dependent generation of cytotoxic oxidative stress.[11]

See also[edit]

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Hedyotis diffusa-Oldenlandia Diffusa kháng Bel-7402

Anti-tumor activity and mechanism of the extracts of Oldenlandia Diffusa on Bel-7402 cell in vitro

Hedyotis diffusa - Oldenlandia Diffusa  kháng Bel-7402

From Wikipedia, the free encyclopedia
Hedyotis diffusa
Oldenlandia diffusa.jpg
Scientific classification
Kingdom:Plantae
(unranked):Angiosperms
(unranked):Eudicots
(unranked):Asterids
Order:Gentianales
Family:Rubiaceae
Genus:Hedyotis
Species:H. diffusa
Binomial name
Hedyotis diffusa
Willd.
Hedyotis diffusa (Chinese: 白花蛇舌草; pinyin: báihuā shéshécǎo; literally: "white flower snake-tongue grass", sometimes abbreviated to 蛇舌草 shéshécǎo[1]) is a kind of herb used in traditional Chinese medicine. It is sometimes combined with Siraitia grosvenorii (simplified Chinese: 罗汉果; traditional Chinese: 羅漢果; pinyin: luóhànguǒ) to make hot drinks like Lohoguo of Guongsei (simplified Chinese: 罗汉果蛇舌草精; traditional Chinese: 羅漢果蛇舌草精; pinyin: luóhànguǒ shéshécǎo jīng) or Luohanguo Pearl and Sheshecao Beverage.[2]
Wild Hedyotis diffusa can be found in China, Japan, and Nepal.

References[edit]

  1. Jump up^ A query for 蛇舌草 on dict.cn gives the definition HERBA HEDYOTIS DIFFUSAE
  2. Jump up^ for example "Luohanguo Pearl and Sheshecao Beverage". 2012-07-18. Archived from the original on 2013-01-01.
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Docosahexaenoic acid kháng Bel-7402

[HTML] Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells

Docosahexaenoic acid kháng Bel-7402

From Wikipedia, the free encyclopedia
Docosahexaenoic acid
DHA numbers.svg
Docosahexaenoic-acid-3D-balls.png
Docosahexaenoic-acid-3D-sf.png
Names
IUPAC name
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid; Doconexent
Other names
cervonic acid, DHA
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard100.118.398
PubChem CID
UNII
Properties
C22H32O2
Molar mass328.488 g/mol
Density0.943 g/cm3
Melting point−44 °C (−47 °F; 229 K)
Boiling point446.7 °C (836.1 °F; 719.8 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes verify (what is Yes ?)
Infobox references
DHA's structure is a carboxylic acid (-oic acid) with a 22-carbon chain (docosa- is Greek for 22) and six (hexa-) cis double bonds (-en-);[2] with the first double bond located at the third carbon from the omega end.[3] Its trivial name is cervonic acid, its systematic name is all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n-3) in the nomenclature of fatty acids.
Most of the DHA in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms the further they are up the food chain. DHA is also commercially manufactured from microalgae: Crypthecodinium cohnii and another of the genus Schizochytrium.[4] DHA manufactured using microalgae is vegetarian.[5]
Some animals with access to seafood make little DHA through metabolism, but obtain it in the diet. However, in strict herbivores, and carnivores that do not eat seafood, DHA is manufactured internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants). Limited amounts of eicosapentaenoic and docosapentaenoic acids are possible products of α-linolenic acid metabolism in young women[6] and men,[7] and though DHA is difficult to detect above dietary background in males compared with females, this illustrates the importance of DHA production for the developing fetus and healthy breast milk.[8] Rates of conversion are 15% higher for women, with those taking oral contraceptives demonstrating 10% higher DHA levels.[9]
DHA is a major fatty acid in brain phospholipids and the retina. While the potential roles of DHA in the mechanisms of Alzheimer's disease are under active research,[10] studies of fish oil supplements, which contain DHA, have failed to support claims of preventing cardiovascular diseases.[11][12][13]

Central nervous system constituent[edit]

DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of the weight of a neuron's plasma membrane is composed of DHA.[14] DHA is richly supplied during breastfeeding, and DHA levels are high in breastmilk regardless of dietary choices.[citation needed]
DHA modulates the carrier-mediated transport of choline, glycine, and taurine, the function of delayed rectifier potassium channels, and the response of rhodopsincontained in the synaptic vesicles, among many other functions.[15]
DHA deficiency is associated with cognitive decline.[16] Phosphatidylserine (PS) controls apoptosis, and low DHA levels lower neural cell PS and increase neural cell death.[17] DHA levels are reduced in the brain tissue of severely depressed patients.[18][19]

Metabolic synthesis[edit]

In humans, DHA is either obtained from the diet or may be converted in small amounts from eicosapentaenoic acid (EPA, 20:5, ω-3) via docosapentaenoic acid (DPA, 22:5 ω-3) as an intermediate.[6][7] This synthesis had been thought to occur through an elongation step followed by the action of Δ4-desaturase.[7] It is now considered more likely that DHA is biosynthesized via a C24 intermediate followed by beta oxidation in peroxisomes. Thus, EPA is twice elongated, yielding 24:5 ω-3, then desaturated to 24:6 ω-3, then shortened to DHA (22:6 ω-3) via beta oxidation. This pathway is known as Sprecher's shunt.[20][21]

Metabolism[edit]

DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others.[22]
The enzyme CYP2C9 metabolizes DHA to epoxydocosapentaenoic acids (EDPs; primarily 19,20-epoxy-eicosapentaenoic acid isomers [i.e. 10,11-EDPs]).[23]

Potential health effects[edit]

Neurological research[edit]

Large-scale human trials showed that DHA did not slow decline of mental function in elderly people with mild to moderate Alzheimer's disease.[24]
In one preliminary study, algal DHA taken for six months decreased heart rate and improved memory and learning in healthy, older adults with mild memory complaints.[25] In another early-stage study, higher DHA levels in middle-aged adults was related to better performance on tests of nonverbal reasoning and mental flexibility, working memory, and vocabulary.[26]
One study found that the use of DHA-rich fish oil capsules did not reduce postpartum depression in mothers or improve cognitive and language development in their offspring during early childhood.[27] Another systematic review found that DHA had no significant benefits in improving visual field in individuals with retinitis pigmentosa.[28] A 2017 pilot study found that fish oil supplementation reduced the depression symptoms emphasizing the importance of the target DHA levels.[29]

Pregnancy and lactation[edit]

It has been recommended to eat foods which are high in omega-3 fatty acids for women who want to become pregnant or when nursing.[30] A working group from the International Society for the Study of Fatty Acids and Lipids recommended 300 mg/day of DHA for pregnant and lactating women, whereas the average consumption was between 45 mg and 115 mg per day of the women in the study, similar to a Canadian study.[31] Despite these recommendations, recent evidence from a trial of pregnant women randomized to receive supplementation with 800 mg/day of DHA versus placebo, showed that the supplement had no impact on the cognitive abilities of their children at up to seven years follow-up.[32]

Other research[edit]

In one preliminary study, men who took DHA supplements for 6–12 weeks had lower blood markers of inflammation.[33]

Nutrition[edit]

Algae-based DHA supplements
Ordinary types of cooked salmon contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams.[34] Additional rich seafood sources of DHA include caviar (3400 mg per 100 grams), anchovies (1292 mg per 100 grams), mackerel (1195 mg per 100 grams), and cooked herring (1105 mg per 100 grams).[34]

Discovery of algae-based DHA[edit]

In the early 1980s, NASA sponsored scientific research on a plant-based food source that could generate oxygen and nutrition on long-duration space flights. Certain species of marine algae produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA and arachidonic acid,[35] present in some health supplements.

Use as a food additive[edit]

DHA is widely used as a food supplement. It was first used primarily in infant formulas.[36] In 2004, the US Food and Drug Administration endorsed qualified health claims for DHA.[37]
Some manufactured DHA is a vegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3s such as EPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive.[38]

Studies of vegetarians and vegans[edit]

Main article: Vegetarian nutrition § Omega-3 fatty acids
Vegetarian diets typically contain limited amounts of DHA, and vegan diets typically contain no DHA.[39] In preliminary research, algae-based supplements increased DHA levels.[40] While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans, breast milk levels remain a concern for supplying adequate DHA to the developing fetus.[39]

DHA and EPA in fish oils[edit]

Fish oil is widely sold in capsules containing a mixture of omega-3 fatty acids, including EPA and DHA. Oxidized fish oil in supplement capsules may contain lower levels of EPA and DHA.[41][42]

Hypothesized role in human evolution[edit]

An abundance of DHA in seafood has been suggested as being helpful in the development of a large brain,[43] though other researchers claim a terrestrial diet could also have provided the necessary DHA.[44]

See also[edit]

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