General

Scientific Names: Dichroa febrifuga Lour.

Common Names: Huang Chang Shan, Hu Cao, Heng Shan, Chang Shan, Sheng Chang Shan, Ji Gu Chang Shan, Chao Chang Shan, Jiu Chang Shan, Cu Shang Shan, Shu Chang Shan.

BOTANICAL:

来 源： 为双子叶植物药虎耳草科植物黄常山的根。

植物特征： 落叶灌木，小枝常有4钝棱，疏生黄色短毛。叶对生，椭圆形或倒卵状长圆形，边缘有细锯齿，幼时两面均被棕黄色短毛；叶柄长1．5～5cm，有时疏生短柔毛。伞房状圆锥花序，花序轴与花梗均有毛；花蓝色，萼筒5～6齿裂；花瓣5～6，反折；雄蕊10～20，花柱4～6，初时基部连合。浆果几完全下位，深蓝色，有宿存萼齿和花柱。花期5～7月，果期8～9月。

Shrubs 1-2 m tall. Branchlets, petioles, and veins glabrous or crisped pubescent. Petiole 1.5-5 cm; leaf blade sometimes purplish abaxially, elliptic, obovate, elliptic-oblong, or lanceolate, 6-25 × 2-10 cm, papery, abaxially glabrous or crisped pubescent along veins, rarely sparsely hirsute, adaxially glabrous, secondary veins 8-10 on both sides of midvein, base cuneate, margin serrate to coarsely so, rarely undulate, apex acute to acuminate. Inflorescence a corymbose panicle, 3-20 cm. Flower buds obovoid, 6-10 mm; pedicel 3-5 mm. Calyx lobes 4-6, broadly deltoid, apex acute. Petals reflexed at maturity, blue or white, oblong-elliptic, slightly fleshy. Stamens 10-20; filaments connate when young, free at maturity, filiform; anthers ellipsoid. Ovary inferior to 3/4 so. Styles 4(-6), clavate; stigma oblong. Berry dark blue when mature, 3-7 mm in diam. Seeds ca. l mm. Fl. Feb-Apr, fr. May-Aug.

生药材鉴定： 干燥的根圆柱形，常分歧，弯曲扭转，长10～15厘米，直径约0．3～2厘米。表面黄棕色，有明显的细纵纹及支根痕迹，栓皮易剥落，显出淡黄色木质部。质坚硬，折断时有粉飞出。横断面黄白色，用水湿润后可见明显的类白色射线，放射状排列。根茎类圆柱形而近块状。横断面除中央有髓外，其他均与根的横断面相同。气微弱，味苦。以质坚实而重、形如鸡骨，表面及断面淡黄色、光滑者为佳，根粗长顺直、质松、色深黄、无苦味者不可入药。

Pharmacology

化学成分: 根含总生物碱约0.1%，其中有常山碱（常山碱乙，febrifugin,β-dichroine）、异常山碱（常山碱甲，isofebrifugin,α-dichroine）及常山碱丙（γ-dichroine），为抗疟有效成分。另含常山次碱（dichroidine）、4-喹唑酮（4-quinazolone）及一种吸湿性生物碱。此外。尚含有两种中性物质：伞形花内酯（常山素Ａ，unbeliferone,dichrin A,7- hydroxycoumarin）、常山素Ｂ（dichrin B）。

Efficacy

Quinazolinone type alkaloids, febrifugine (1) and isofebrifugine (2), isolated from Dichroa febrifuga roots, show powerful antimalarial activity against Plasmodium falciparum. Unfortunately, their emetic effect and other undesirable side effects have precluded their clinical use for malaria. Because of their antimalarial potency, analogues were searched for, with the goal of preserving the strong antimalarial activity, while dramatically reducing side effects. We expected that compounds useful in drug development would exist in metabolites derived from 1 and Df-1 (3), the condensation product of 1 with acetone, by mouse liver S9. Feb-A and -B (4 and 5) were isolated as the major metabolites of 1. In addition to 4 and 5, feb-C and -D (6 and 7) were also purified from the metabolic mixture of 3. Compounds 4 and 5 were compounds oxidized at C-6 and C-2 of the quinazolinone ring of 1, respectively. Compounds 6 and 7, derived from 3, also bear febrifugine type structures in which the 4' '- and 6' '-positions of the piperidine ring of 1 were oxidized. In vitro antimalarial and cytotoxic tests using synthetically obtained racemic 4-6 and enantiomerically pure 7 demonstrated that 4 and 6 had antimalarial activity against P. falciparum, of similar potency to that of 1, with high selectivity. The antimalarial activity of 5 and 7, however, was dramatically decreased in the test. The in vitro antimalarial activity of analogues 22 and 43, which are stereoisomers of 4 and 6, was also evaluated, showing that 22 is active. The results suggest that basicity of both the 1- and the 1' '-nitrogen atoms of 1 is crucial in conferring powerful antimalarial activity. Racemic 4 and 6 exhibited powerful in vivo antimalarial activity against mouse malaria P. berghei, and especially, no serious side effects were observed with 4. Thus, the metabolite 4 appears to be a promising lead compound for the development of new types of antimalarial drugs. (source)

常山总碱对小白鼠艾氏腹水癌、肉瘤-180及腹水型肝癌 均有抑制作用。常山碱乙对艾氏腹水癌细胞有明显毒杀作用，其抑制率为50-100%，对多种实验性肿瘤有一定疗效，其抑制率：小鼠艾氏腹水瘤实体型为 45%；小鼠肉瘤-180为45%；小鼠黑色素瘤为75%；小鼠腹水肝癌为55%；大鼠肉瘤-45为30%；小鼠瓦克癌为45%。体外试验常山碱丙对艾氏 癌细胞有一定杀灭作用。 (source)

IN VITRO:

1. Hirai S, et al., Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite. J Med Chem. 2003 Sep 25; 46(20):4351-9.
   
   
   
   
   
   

Safety

宜忌: 正气虚弱，久病体弱者忌服。《雷公炮炙论》：“勿令老人、久病服之，切忌也。” 《本草经集注》：“畏玉札。” 《药性论》：“忌葱。” 《本草蒙筌》：“忌鸡肉。” 《本草经疏》：“疟非由于瘴气及老痰积饮所致者勿用。”