General

Scientific Names: Rubia cordifolia L.

Common Names: Qian Cao, Si Lun Cao, La La Man, Xiao Huo Xue, Guo Shan Teng.

BOTANICAL:

来 源： 为茜草科多年生攀援草本植物茜草Rubia cordifolia L. 的根及根茎。

植物特征： 多年生攀援草本。茎四棱形，有的沿棱有倒刺。叶4片轮生，其中1对较大而具长柄，卵形或卵状披针形，长2.5~6cm或更长，宽1~3cm或更宽；叶缘和背脉有源小倒刺。聚伞花序顶生或腋生；花小，萼齿不明显，花冠绿色或白色，5裂，有缘毛。果肉质，小形，熟时紫黑色。花果期9~10月。
生于山坡岩石旁或沟边草丛中。主产安微、河北、陕西、河南、山东。
。

生药材鉴定： 根茎呈不规则结节状，上侧有茎基，下侧丛生粗细不等的根。根呈圆柱子形，波状弯曲，长工10~25cm，直径0.2~1cm,表面红棕色或暗棕色，具细纵纹及少数细根痕。质脆，断面平坦，皮部紫红色，木部浅黄红色。气微。味微苦。

Pharmacology

化学成分: 根含多种羟基蒽醌衍生物，如茜草素（alizarin）、异茜草素（purpuro-xanthin）、羟基茜草素（purpurin）、伪羟基茜草素（pseudopurpurin）、茜草酸(munjistin)、茜草甙(rubia,ruberythric acid)、大黄素甲醚等，又分离得升白活性成分茜草萘酸甙Ⅰ及Ⅱ，其甙元为茜草萘酸。

Efficacy

抗肿瘤作用： 茜草属活血化瘀抗癌中药，茜草中提取抗癌活性较强的成分，如茜草根中提出一种环状肽（RA），治疗小鼠白血病，腹水癌，大肠癌，肺癌，防止癌转移，效果近似长春新碱，丝裂霉素C，阿霉素，而对正常细胞损伤小。

The antiviral activity in the roots of Rubia cordifolia was examined, and three naphthohydroquinones, furomollugin (1), mollugin (2), and rubilactone (3), were isolated from it. Compounds 1 and 2 strongly suppressed the secretion of hepatitis B surface antigen (HBsAg), both with IC50 = 2.0 micrograms/mL, in human hepatoma Hep3B cells while having little effect on the viability of the cells. Evaluation of structurally related derivatives of 1 and 2 revealed that a 6-hydroxy group and a pyran or furan ring contribute to this suppressive effect. (Source)

An antitumor substance, RA-700, isolated from Rubia akane or Rubia cordifolia has the novel structure. Phase I clinical study was conducted by the RA-700 clinical study group consisting of 6 institutions. A single dose administration and 5-day schedule administration were evaluated with 14 patients respectively. RA-700 was given from 0.2 to 1.4 mg/m2 in single i.v. dose study, from 0.4 to 2.0 mg/m2 in 5-day i.v. schedule study. Nausea and vomiting, fever, stomachache, mild hypotension and slight abnormality of electric-cardiogram were observed as the toxicities. In pharmacokinetic study, the elimination half-lives (t1/2) of RA-700 in plasma were 55 min, of alpha-phase and 3.9 hrs. of beta-phase by single dose study, and 23-25 min. of alpha-phase and 6-14 hrs. of beta-phase by 5-day schedule study. Accumulation was not found by 5-day schedule administration, and metabolite were not observed in plasma and urine. It seems that RA-700 is metabolized by the liver and excreted in the feces. In conclusion, the maximum tolerated dose was 1.4 mg/m2 for 5-day schedule administration. (Source)

The antitumor activity of RA-700, a cyclic hexapeptide isolated from Rubia Cordifolia, was evaluated in comparison with deoxy-bouvardin and vincristine (VCR). As regards the proliferation of L1210 cultured cells, the cytotoxicity of RA-700 was similar to that of VCR but superior to that of deoxy-bouvardin. The IC50 value of RA-700 was 0.05 mcg/ml under our experimental conditions. RA-700 inhibited the incorporation of 14C-leucine at a concentration at which no effects were observed on the incorporation of 3H-thymidine and 3H-uridine in L1210 culture cells in vitro. The antitumor activity of RA-700 was similar to that of deoxy-bouvardin and VCR against P388 leukemia. Daily treatment with RA-700 at an optimal dose resulted in 118% ILS. As with deoxy-bouvardin and VCR, the therapeutic efficacy of RA-700 depends on the time schedule. RA-700 showed marginal activity against L1210 leukemia (50% ILS), similar to that of deoxy-bouvardin but inferior to that of VCR. RA-700 inhibited Lewis tumor growth in the early stage after tumor implantation, whereas deoxy-bouvardin and VCR did not. As regards toxicity, a slight reduction of peripheral WBC counts was observed with the drug, but no reduction of RBC and platelet counts. BUN, creatinine, GPT and GOT levels in plasma did not change with the administration of the drug. (Source)

Anti-tumour activity of RC-18, a pure isolate from Rubia cordifolia was repeatedly tested in different sets of experiments on a spectrum of experimental murine tumours, viz. P388, L1210, L5178Y, B16 melanoma, Lewis lung carcinoma and sarcoma-180. RC-18 exhibited significant increase in life span of ascites leukaemia P388, L1210, L5178Y and a solid tumour B16 melanoma. However, it failed to show any inhibitory effect on solid tumours, Lewis lung carcinoma and sarcoma 180. Promising results against a spectrum of experimental tumours suggest that RC-18 may lead to the development of a potential anti-cancer agent. (Source)

IN VITRO:

1. Wakita Ki, et al., Antitumor bicyclic hexapeptide RA-VII modulates cyclin D1 protein level. Anticancer Drugs. 2001 Jun; 12(5):433-9.
2. Ho LK, et al., Inhibition of hepatitis B surface antigen secretion on human hepatoma cells. Components from Rubia cordifolia. J Nat Prod. 1996 Mar; 59(3):330-3.
3. Itokawa H, et al., Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull (Tokyo). 1993 Oct; 41(10):1869-72.
4. Takeya K, et al., Two antitumour bicyclic hexapeptides from Rubia cordifolia. Phytochemistry. 1993 Jun; 33(3):613-5.
5. Morita H, et al., New antitumor bicyclic hexapeptides, RA-XI, -XII, -XIII and -XIV from Rubia cordifolia. Chem Pharm Bull (Tokyo). 1992 May; 40(5):1352-4.
6. Itokawa H, et al., Cell growth-inhibitory effects of derivatives of antitumor cyclic hexapeptide RA-V obtained from Rubiae radix (V). Gann. 1984 Oct; 75(10):929-36.
7. Adwankar MK, et al., Effect of RC-18, a new anticancer principle isolated from Rubia cordifolia, Linn. on cell cycle of P388 tumour system. Biomed Pharmacother. 1982 Mar; 36(2):104-5.
8. Adwankar MK, et al., Anti-cancer activity of the extracts of Rubia cordifolia Linn. (NSC b668893). Indian J Exp Biol. 1980 Jan; 18(1):102.
   
   
   

IN VIVO:

1. Kato T, et al., Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide. Anticancer Res. 1987 May-Jun; 7(3 Pt B):329-34.
2. Adwankar MK, et al., In vivo anti-cancer activity of RC-18: a plant isolate from Rubia cordifolia, Linn. against a spectrum of experimental tumour models. Chemotherapy. 1982; 28(4):291-3.
   
   

CLINICAL:

1. Yoshida F, et al., [Study of cardiac function in first stage examination of RA-700. RA-700 Clinical Study Group]. Gan To Kagaku Ryoho. 1994 Feb; 21(2):199-207. Japanese.
2. Majima H, et al., [Phase I Study of RA-700. RA-700 Clinical Study Group]. Gan To Kagaku Ryoho. 1993 Jan; 20(1):67-78. Japanese.
   

Safety