Ethnopharmacological relevance: With theprevalentuseofhighlyactiveantiretroviraltherapy(HAART)
for AIDSpatientssince1996,themortalityofHIV/AIDSpatientshasbeenremarkablydecreased.With
long-term useofHAART,drugresistanceandsideeffectsofantiretroviralshavebeenfrequentlyreported,
which notonlyreducetheefficacy,butalsodecreasesthetoleranceofpatients.Traditionalherbal
medicine hasbecomemorepopularamongHIV/AIDSpatientsasadjuvanttherapytoreducethese
adverse effectsofHAART.SHformulaisaChineseherbalformulaconsistingof five traditionalChinese
herbs including Morus alba L., Glycyrrhizaglabra L., Artemisia capillaris Thumb., Astragalusmembranaceus
Bge., and Carthamus tinctorius L. SHformulaisclinicallyusedforHIVtreatmentinThailand.However,the
possible pharmacokineticinteractionsbetweentheseChineseherbsandantiretroviraldrugshavenot
been welldocumented.Theaimofthisstudywastoinvestigatethepotentialherb-druginteraction
between SHherbalChineseformulaandtheantiretroviraldrugatazanavir(ATV).
Materials andmethods: The combinationeffectofSHformulaandATVonHIVproteasewasstudiedin
HIV-1 proteaseinhibitionassay in vitro. TheinhibitionofSHformulaonratCYP3A2wasassessedby
detecting theformationof10–OH midazolamfrommidazolaminratlivermicrosomes in vitro. The in vivo
pharmacokinetic interactionbetweenSHformulaandATVwasinvestigatedbymeasuringtime-
dependent plasmaconcentrationsofATVinmaleSprague–Dawleyratswithliquidchromatography–
mass spectrometry.
Results: Throughthe in vitro HIV-1 proteaseinhibitionassay,combinationofSHformula(41.7–166.7 μg/
ml) andATV(16.7–33.3 ng/ml)showedadditiveinhibitiononHIV-1proteaseactivitythanSHformulaor
ATVusedalone. In vitro incubation assayindicatedthatSHformulashowedaweakinhibition
(IC50¼231.2 mg/ml; Ki¼98.2 mg/ml) onCYP3A2activityinratlivermicrosomes. In vivo pharmacokinetic
study demonstratedthatSHformuladidnotaffectthemetabolismofATVinrats.
Conclusions: Our studydemonstratedforthe first timethatthereisnometabolism-basedherb-drug
interactionbetweenSHformulaandATVinrats,butthiscombinationenhancestheinhibitionpotentials
against HIVproteaseactivity.Thisobservationmaysupportthecombinationaluseofanti-HIVtreatment
in human.
Ethnopharmacological เกี่ยวข้อง: มี theprevalentuseofhighlyactiveantiretroviraltherapy(HAART)สำหรับ AIDSpatientssince1996,themortalityofHIV/AIDSpatientshasbeenremarkablydecreased.Withระยะยาว useofHAART, drugresistanceandsideeffectsofantiretroviralshavebeenfrequentlyreportedที่ notonlyreducetheefficacy, butalsodecreasesthetoleranceofpatients Traditionalherbalยา hasbecomemorepopularamongHIV/AIDSpatientsasadjuvanttherapytoreducetheseร้าย effectsofHAART.SHformulaisaChineseherbalformulaconsistingof ห้า traditionalChineseสมุนไพรรวมทั้งหม่อน Glycyrrhizaglabra L., Artemisia capillaris นิ้วหัวแม่มือ AstragalusmembranaceusBge และดอกยา L. SHformulaisclinicallyusedforHIVtreatmentinThailand.However,thepharmacokineticinteractionsbetweentheseChineseherbsandantiretroviraldrugshavenot เป็นไปได้welldocumented แล้ว Theaimofthisstudywastoinvestigatethepotentialherb-druginteractionระหว่าง SHherbalChineseformulaandtheantiretroviraldrugatazanavir(ATV)Andmethods วัสดุ: combinationeffectofSHformulaandATVonHIVproteasewasstudiedin การการเพาะเลี้ยง proteaseinhibitionassay เอชไอวี-1 TheinhibitionofSHformulaonratCYP3A2wasassessedbyตรวจสอบใน midazolamfrommidazolaminratlivermicrosomes theformationof10 – OH ในสัตว์ทดลองpharmacokinetic interactionbetweenSHformulaandATVwasinvestigatedbymeasuringtime-อ้างอิง plasmaconcentrationsofATVinmaleSprague-Dawleyratswithliquidchromatography-โตรเมทรีผลลัพธ์: Throughthe ในหลอดเชื้อเอชไอวี-1 proteaseinhibitionassay, combinationofSHformula (41.7 – 166.7 μg /andATV มล) (16.7-33.3 ng/ml) showedadditiveinhibitiononHIV-1proteaseactivitythanSHformulaorATVusedalone บ่มเพาะเลี้ยง assayindicatedthatSHformulashowedaweakinhibition(IC50¼231.2 mg/ml Ki¼98.2 mg/ml) onCYP3A2activityinratlivermicrosomes ใน vivo pharmacokineticศึกษา demonstratedthatSHformuladidnotaffectthemetabolismofATVinratsบทสรุป: เรา studydemonstratedforthe แรก timethatthereisnometabolism-basedherb-ยาเสพติดinteractionbetweenSHformulaandATVinrats, butthiscombinationenhancestheinhibitionpotentialsกับ HIVproteaseactivity.Thisobservationmaysupportthecombinationaluseofanti-HIVtreatmentในมนุษย์
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