Croton
1、 Croton pharmacopoeia standard       This product is the dried and mature fruit of croton tiglium L., a Euphorbiaceae plant. The fruits are harvested when they are ripe in autumn, stacked for 2-3 days, spread out, and dried.
      [character] this product is oval, generally with three edges, 1.8 ~ 2.2cm long and 1.4 ~ 2cm in diameter. The surface is grayish yellow or slightly deep, rough, with 6 longitudinal lines, the top is flat cut, and the base has fruit stem marks. . The seeds are slightly oblate oval, 1.2-1.5cm long, 0.7-0.9cm in diameter, brown or grayish brown on the surface, with a small punctate hilum and caruncle scar on one end and a slightly concave commissure on the other end, with a raised seed ridge between them; The exotesta is thin and brittle, and the endotesta is white thin film; The seed kernel is yellowish white and oily. It has slight air and spicy taste.
      [identification] (1) cross section of this product: the exocarp is a row of epidermal cells, covered with multicellular stellate hairs. There are more than 10 rows of parenchyma cells scattered with stone cells, calcium oxalate crystals or cluster crystals on the outer side of mesocarp; There are about 4 rows of fibrous stone cells in the middle; The inner side is a series of parenchymal cells. The endocarp is composed of 3-5 rows of fibrous sclerenchymal cells. The seed coat epidermal cells are composed of a row of radially elongated rectangular cells, under which is a row of thick walled grid cells with linear lumen and slightly expanded outer end.
      (2) Take the kernel of this variety, grind it, take 0.1g, add 10ml of petroleum ether (30 ～ 60 ℃), sonicate it for 20 minutes, filter it, and the filtrate is used as the test solution. Another 0.1g Croton reference drug was taken and prepared into the reference drug solution by the same method. . In the chromatogram of the test sample, spots of the same color appear on the corresponding position of the chromatogram of the control medicinal material.
      [check] moisture   .
      Total ash   .
      [content determination] fatty oil   Take 1g of crude powder of this product, weigh accurately, put it into Soxhlet extractor, add appropriate amount of ether, heat and reflux extraction (8 hours) until the fatty oil is extracted, collect the extraction solution, put it into an evaporating dish that has been dried to constant weight, evaporate it at low temperature on a water bath, dry it at 100 ℃ for 1 hour, move it into a dryer, cool it for 30 minutes, weigh accurately, calculate, and get it.
      According to the calculation of dry products, the fatty oil content of this product shall not be less than 22.0%.
      ; Determine according to high-performance liquid chromatography (general rule 0512).
      Chromatographic conditions and system suitability test   Octadecylsilane bonded silica gel was used as filler; The mobile phase was acetonitrile methanol water (1:4:95); .
      Preparation of reference solution   .
      Preparation of test solution   Take about 0.3g of this variety of kernel powder (through No. 3 screen), weigh it accurately, put it in Soxhlet extractor, add 50ml of ether, heat and reflux for 3 hours, discard the ether solution, volatilize the solvent from the drug residue, transfer it together with the filter paper cylinder into a corked conical bottle, add 50ml of water precisely, weigh it, ultrasonic treatment (power 300W, frequency 24khz) for 20 minutes, cool it, weigh it again, make up the lost weight with water, shake it well, filter it.
      Assay   Precisely suck 10 μ l of the reference solution and 10 μ l of the test solution respectively, inject them into the liquid chromatograph, and determine.
      According to the calculation of dry product, the content of crotonoside (c10h13n5o5) shall not be less than 0.80%.
      Decoction pieces
      [processing] raw croton   .
      [nature, taste and meridian tropism] pungent, hot; It is highly toxic. Return to stomach and large intestine.
      [function and indications] external use ulcer. For scabies, scabies, warts and nevi.
      [usage and dosage] for external use, apply proper amount to the affected area after grinding, or mash it and rub it with gauze.
      [note] it is forbidden for pregnant women; It should not be used with Petunia.
      [storage] store in a cool and dry place.


2、 Chemical constituents of Croton
The seed contains 34% - 57% croton oil and about 18% protein.

Crotonicacid is contained in croton oil,Crotonic acid（tiglicacid）， frompalmitic acidGlycerides, including stearic acid, oleic acid, crotonolic acid, crotonolic acid, etc., phorbol, and 16 crotonol diester compounds, namely phorbol-12-myristate-13-acetate, phorbol-12-caprate-13-acetate, phorbol-12-laurate-13-acetate, phorbol-12-palmitate-13-acetate rbol-12-palmitate-13-acetate), Phorbol-12-a-methylbutyrate-13-laurate, phorbol-12-a-methylbutyrate-13-caprate, phorbol-12-a-methyl-butyrate-13-laurate, phorbol-12-acetate-13-laurate, phorbol-12-acetate-13-caprate, phorbol-12-acetate-13-caprate phorbol-12-tiglate-13-caprate, Phorbol-12-tiglate-13-caprylenate, phorbol-12-a-methylbutyrate-13-caprylenate, phorbol-12-tiglate-13-laurate, phorbol-12-tiglate-13-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-12-tiglate-13-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-13-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-13-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, phorbol-12-butyrate, Phorbol-12-benzoate-13-benzoate, phorbol-4-methoxy-12-myris-tate-13-acetate, and 4-deoxy-4a-phorbol are triester compounds. The seed kernel also contains a toxic globulin, crotin, from which crotin Ⅰ and Ⅱ were isolated. Their relative molecular weights are 40KD and 15kD, and their isoelectric points are 8.0 and 6.7, respectively. In addition, it contains cocarcinogenc-3,Crotonoside（crotonoside）， Croton alkaloid isoguanine,β - sitosterol（β-sitosterol）， Amino acids and enzymes, etc.

3、 Pharmacological action of Croton
1. irritating effect on skin and mucosa: croton oil is the most intense laxative. It can produce burning sensation and vomiting of oral and gastric mucosa when taken orally from half to one drop. There are many times of massive watery diarrhea within 1/2-3 hours, accompanied by severe abdominal pain and tenesmus, resulting in severe oral irritation and gastroenteritis symptoms. Croton oil for external use can irritate the skin, cause redness, and can develop into pustules or even necrosis; Diluted with olive oil can be used as an irritant, but it is more dangerous. Mice injected with 5% croton oil subcutaneously on the same day, 1 day or 2 days before the Japanese encephalitis virus injection, compared with the control group injected with the virus alone, the mortality was reduced and the survival time was prolonged. The effect may be produced through the nervous system, or it may directly affect the virus toxicity.

2. effect on digestive tract: 2.1. defecation effect of Croton on different constipation mice: the mice were copied into the constipation models of excess heat type, dry knot type, cold knot type and spleen stomach deficiency cold type, and were given Croton Decoction respectively, and compared with the unmodeled control. The experimental results showed that Croton could significantly prolong the defecation time of spleen stomach deficiency cold type constipation mice, with significant difference compared with the control group (p< 0.05).

2.2. effect on gastrointestinal tract and secretion of bile and pancreatic juice: croton oil and resin contained in it can react with alkaline solution in the intestine after oral administration to precipitate Croton oleic acid and crotonol diester compounds, which can acutely stimulate the intestinal wall, cause strong peristalsis and cause severe diarrhea. Croton decoction has obvious excitatory effect on isolated rabbit intestinal muscle, which is not antagonized by atropine. Croton oil emulsion also has an excitatory effect on the intestine of rabbits and dogs, while a large dose has an inhibitory effect, and it is not relieved by acetylcholine, pilocarpine or barium chloride, so croton oil directly acts on the intestinal muscle. . The experiment of gall flaccid rabbits showed that Croton water could increase the secretion of bile and pancreatic juice.

3. effects on circulatory system and respiratory system: 3.1. croton oil can reflexively elevate blood pressure by acting on chemoreceptors in the hind limbs and intestines of animals ex vivo but with nerves.

. It can agglutinate blood cells of cattle, sheep, pigs and frogs. PMA (phorbolmyristateacetcmlibate), the active ingredient in croton oil, can increase the concentration of cyclic guanosine monophosphate (CGMP) in platelets. It is a powerful platelet agglutinant.

; Subcutaneous injection can accelerate respiratory rate and reduce respiratory exchange volume. Although hemoglobin increased, arterial oxygen content was still mildly reduced.

4. effect of anti pathogen: Croton decoction has certain antibacterial effect on influenza bacilli, Pseudomonas aeruginosa, Staphylococcus aureus and diphtheria bacilli. Croton oil preparation can reduce the mortality and prolong the survival time of mice infected with epidemic encephalitis B.

5. analgesic effect: tail pressing method in rats, hot plate method in mice and benzophenone writhing test showed that croton oil orally, subcutaneously or intraperitoneally could increase the pain threshold by 50-70%, and its analgesic mechanism may be related to the local stimulation of croton oil.

6. anti tumor and tumor promoting effects: Croton extract has obvious inhibitory effects on S180 solid type and S180 ascites type of mouse sarcoma, U14 solid type and U14 ascites type of mouse cervical cancer, and Ehrlich ascites cancer. Croton injection has tumor killing effect in vitro. Crotonol diester has a certain inhibitory effect on mouse lymphocytic leukemia P388. . Therefore, Croton is considered to contain anticancer active substances. On the other hand, croton oil and crotonol can promote carcinogens to produce tumors. Although croton oil has no carcinogenic effect, it can cause cutaneous papilloma when used with urethane. Croton oil and the acetate salt of its component tetradecanoyl Crotonyl ester (tetcmlibadecaoylphorbol) can cause skin hyperplasia in mice. Crotonyl ester C can change the structure and permeability of mouse embryonic fibroblast membrane. These changes may be related to promoting tumorigenesis. Croton oil and bovine immunoglobulin antigen injected into guinea pigs can inhibit the production of antibodies and delay the allergic reaction to antigens. Crotonol has stronger immunosuppressive effect than croton oil, and this immunosuppressive effect may also be one of the reasons for the formation of tumors. It is also believed that the promotion of tumor may be closely related to the inhibition of cell differentiation by Crotonyl ester, which can elevate ornithine decarboxylase, a fibrinogen activator.

7. other functions: Croton has the effect of killing oncomelania snails. The seed kernel is the most effective, followed by the inner shell, and the shell is ineffective. The acetone extract of Croton is very toxic to goldfish. The salt water extract of Croton can be used to remove wild fish in the domestic fish pond (before stocking domestic fish), but the effect is not as good as quicklime. The intravenous injection of Croton aqua in rabbits can increase the secretion of bile and pancreatic juice. It has no diuretic effect on rabbits with ureteral flaccidity, and has a mild inhibitory effect on isolated rabbit uterus. Croton oil can cause local release of histamine in rats and skin and increase the secretion of adrenocortical hormone. Croton toxin protein can inhibit the synthesis of protein.