safflower
1、         This product is the dried flower of Carthamus tinctorius L., a composite plant. In summer, flowers are picked when they turn from yellow to red, dried in the shade or in the sun.
        [character]   This product is a tubular flower without ovary, 1 ~ 2cm long. The surface is red, yellow or red. The corolla tube is slender, the apex is 5-lobed, the lobes are narrow strip, 5-8mm long; the stamens are 5, and the anthers aggregate into a tube, yellow white; The stigma is long cylindrical, and the top is slightly bifurcated. . The smell is slightly fragrant and the taste is slightly bitter.
        [identification]   (1) The powder of this product is orange yellow. . The outer wall processes of epidermal cells at the top of corolla lobes were short fluffy. The epidermal cells of the stigma and upper part of the style differentiate into conical single-cell hairs, and the apex is pointed or slightly blunt. The pollen grains are round, oval or olive shaped, with a diameter of about 60 μ m, with three germination pores, and toothed protrusions on the outer wall. Calcium oxalate crystals exist in parenchyma cells with a diameter of 2-6 μ M.
        (2) Take 0.5g of this product powder, add 5ml of 80% acetone solution, tightly plug, shake for 15 minutes, stand still, and take the supernatant as the test solution. . According to the test of thin-layer chromatography (general rule 0502), suck 5 μ l of the above two solutions, respectively dot them on the same silica gel h thin-layer plate, use ethyl acetate formic acid water methanol (7:2:3:0.4) as the developing agent, develop, take out and dry. 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]   Impurities shall not exceed 2% (general rule 2301).
        .
        The total ash content shall not exceed 15.0% (general rule 2302).
        Acid insoluble ash content shall not exceed 5.0% (general rule 2302).
        .
        [extract]   It shall be determined according to the cold leaching method under the determination method of water-soluble extract (general rule 2201), and shall not be less than 30.0%.
        [content determination]   Hydroxysafflor yellow a was determined by HPLC (general rule 0512).
        ; Methanol acetonitrile-0.7% phosphoric acid solution (26:2:72) was used as the mobile phase; The detection wavelength was 403nm. The number of theoretical plates should not be less than 3000 according to the peak of hydroxysafflor yellow a.
        Preparation of reference solution   Take an appropriate amount of hydroxysafflor yellow a reference substance, accurately weigh it, add 25% methanol to make a solution containing 0.13mg per IML.
        Preparation of test solution take about 0.4g of powder (passing through No. 3 screen), weigh accurately, place in a corked conical flask, add 50ml of 25% methanol precisely, weigh, sonicate (power 300W, frequency 50KHz) for 40 minutes, cool, weigh again, make up the lost weight with 25% methanol, shake well, filter, and take the filtrate.
        ; 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 hydroxysafflor yellow a (c27h32o16) shall not be less than 1.0%.
        Kaempferol   Determine according to high-performance liquid chromatography (general rule 0512).
        ;   Octadecylsilane bonded silica gel was used as filler; The mobile phase was methanol-0.4% phosphoric acid solution (52:48); The detection wavelength was 367nm. The number of theoretical plates should not be less than 3000 according to the kaempferol peak.
        ; Take an appropriate amount of kaempferol reference substance, accurately weigh it, add methanol to make a solution containing 9 μ g per 1ml.
        Preparation of test solution   Take about 0.5g of this product powder (passing through No. 3 screen), weigh it accurately, place it in a corked conical flask, add 25ml of methanol precisely, weigh it, heat it for 30 minutes, cool it, weigh it again, use methanol to make up the lost weight, shake it well, filter it, accurately measure 15ml of continuous filtrate, place it in a flat bottom flask, add 5ml of hydrochloric acid solution (15 → 37), shake it well, heat it in a water bath for hydrolysis for 30 minutes, immediately cool it, transfer it to a 25ml measuring flask, dilute it with methanol to the scale, shake it well, filter it, and take the continuous filtrate.
        ; 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 kaempferol (c15h10o6) shall not be less than 0.050%.
        [nature, taste and meridian tropism]   Xin, Wen. Heart returning and liver meridian.
        ; Activating blood circulation and dredging channels, dispersing blood stasis and relieving pain. It is used for amenorrhea, dysmenorrhea, lochia, symptomatic lump, chest pain, abdominal pain due to stasis, chest and flank pain, falling and flapping injury, sore swelling and pain.
        [usage and dosage]   3～10g。
        [note]   Caution for pregnant women.
        ; Store in a cool and dry place, damp proof and mothproof.


2、 Chemical constituents of safflower
,Safflower Pigment a（safflow yellow A）[1-3]， Saffromina a[4]. It also contains polyphenols:chlorogenic acid（chlorogenic acid），caffeic acid（caffeic acid）， . It also contains more than 80 volatile components, and the structures of which have been determined are: ethyl acetate, benzene, 1-penten-3-ol, 3-hexanol, 2-Hexanol, (E) - 2-hexenal [(E) - 2-hexenal], 3-methyl butyric acid, 2-methyl butyric acid, ethylbenzene, p-xylene, o-xylene benzene (o-xylene), phenylacetaldehyde, nonanal, terpinen-4-ol, Verbenone, decanal, benzothiazole, (E, e) - 2,4-decadienal [(E, e) - 2,4-decadienal], methyl cinnamate, 1,2,3-trimethoxy-5-methylbenzene, α - (Wanggu) (wangba) ene, 1-tetcmlibadecene, α - Cypress α -cedrene, caryophyllene, (E) - β - farnesene [(E) - β -farnesene], humulene, β -ionone, β -selinene, dihydroac tinidolide, 1-pentadecene, ζ -cadinene, caryophyllene epoxide, 1-Hexadecene, 1,3,5,11-tridecatetraene-7,9-diyne 9-diyne), (E, e, e), (E, Z, e) and (Z, e, e), （Z、Z）-1， , 11-TCMLIBidecaTCMLIBiene-5，7，9-TCMLIBiyen]，（Z、Z）-1， (Z, e) and (E, e) isomers of 8,11-heptadecatcmlibiene [(Z, z) - 1,8,11-heptadecatcmlibiene], 1,3,11-tridecatriene-5,7,9-triayne (1,2,33-tcmlibidecatcmlibiene-5,7,9-tcmlibiyne), （Z、Z、Z）-1， 8,11,14-heptadecatetraene [(Z, Z, z) - 1,8-11,14 hep tadecatetcmlibaene], (z) - 1,11-tridecadiene-3,5,7,9-tetrayne [(z) - 1,3,5-tridecatriene-7, 9-11-triyne] [(E, z) - 1,3,5-tcmlibidecatcmlibiene-7,9,11-tcmlibiyen], 1-heptadecaene, (E) - 1,3,5-tcmlibidecatcmlibiene-7,9,11-tcmlibiyne], 1,3-tcmlibidecatcmlibiene-5,7,9,11-tetrayne (1,3-tcmlibidecadiene-5,7,9-tetcmlibayne), 1,3-tridecadiene-5, 5,7,9-tetrayne [(E) - 1,11-tcmlibidecadiene-3,5,7,9-tetcmlibayne], 1,3-tridecadiene-5,7,9,11-tetrayne (1, 3-tcmlibidecadiene-5, 7, 9, 11 tetcmlibayne) has two isomers (E) and (z), （E、E）-1， 3,5-tridecatriene-7,9,11-triyne [(E, e) - 1,3,5-tcmlibideca-tcmlibiene-7,9,11-tcmlibiyne], 3-methylbutyrate-4,6-decadiyn-1-ol ester (deca-4,6-diyn-1-yl 3-methylbutyrate), 1-tridecane-3,5,7,9,11-pentayne (1-tcmlibidecene-3,5,7,9,11-pentayne)], 3-methylbutyrate acid - (z) - 8-decene-4,6-diynol-1-ester [(z) - 8-decene-4, . The amino acids with benzene ring and sulfur-containing are the least abundant [6]. It also contains rhamnose, arabinose, xylose, glucose, mannose [6], nonacosane,β - sitosterol（β-sitosterol）， ,Myristic acid（myristic acid）， Lauric acid [7], α, γ - dipalmitin, oleic acid, linoleic acid, β - sitosterol-3-o-glucoside [8]. . It also contains propanetcmlibiol - α - l-arabinofuranosyl (1 → 4) - β - d-glucopyrano-side][10], which has the effect of lowering blood pressure.
Neoqianhua bud contains luteolin-7-o-gluco-side, cholesterol,Stigmasterol（stigmasterol），β - sitosterol, lauric acid,Myristic acid, palmitic acid, linoleic acid, stearic acid, arachidic acid [11].

3、 Pharmacological action of safflower
; A large dose has an inhibitory effect on the heart, slowing down the heart rate, weakening the myocardial contractility, and reducing the cardiac stroke volume.
1.2 the experimental study on coronary blood flow shows that safflower water extract and safflower yellow, a water-soluble mixture of safflower, can increase coronary blood flow and myocardial nutrient blood flow; .
1.3 experimental studies on experimental myocardial ischemia and myocardial infarction show that safflower and its preparations have different degrees of antagonism on animal models of experimental myocardial ischemia or myocardial infarction, such as rabbits, rats, dogs, etc. Safflower can protect rats or rabbits from acute myocardial ischemia caused by pituitrin; It can significantly reduce the degree of acute myocardial ischemia in anesthetized dogs caused by repeatedly and briefly blocking coronary blood flow, reduce the scope, slow down the heart rate, and protect the edge of the acute myocardial infarction zone, reduce the infarct scope and reduce the amplitude of ST segment elevation in the ECG of the edge zone, so as to improve the supply and demand relationship of oxygen in ischemic myocardium.
1.4. the study on the effect of Safflower on blood vessels found that if the blood vessels were perfused with Lowe's solution containing trace epinephrine or norepinephrine first, the isolated vascular smooth muscle of animals would contract and maintain a certain degree of vascular tension, resulting in blood blockage and blood stasis that may be similar to human. . It is indicated that the vasodilatory effect of safflower is related to the functional state of blood vessels and the dose of drugs. Its mechanism of action may be that it directly or partially antagonizes the action of a-adrenergic receptor to dilate blood vessels, and has a weak direct vasoconstriction effect.
1.5. effect of Safflower on cerebral edema caused by ischemic stroke in experimental animals: Safflower injection (1ml containing crude drug LG) was administered to 63 Mongolian gerbils by IP at 10g/kg safflower injection 30 minutes before operation, and the operation control group and sham operation group were established to observe the effect of Safflower on ischemic cerebral edema, and the changes of monoamine neurotransmitter content in the same brain region were studied. The results suggest that the mechanism of safflower alleviating ischemic brain edema may be related to its effect on the metabolic disorder of monoamine neurotransmitters in tissues. And further confirmed that safflower can indeed reduce the incidence and mortality of stroke, and has a protective effect on the brain tissue of experimental thoracic infarction animals.
1.6. antihypertensive effect: Safflower decoction, safflower yellow pigment and other preparations have different degrees of rapid antihypertensive effect on anesthetized cats or dogs. The average blood pressure drops by about 20 minutes Hg, and recovers after about 30 minutes.
1.7. the experimental study on the anticoagulant effect of safflower yellow pigment shows that safflower yellow pigment can significantly inhibit ADP induced platelet aggregation in rabbits, and also has a very obvious depolymerization effect on ADP aggregated platelets. When the dose was 0.22g/ml, the aggregation inhibition rate and depolymerization percentage reached 85.9% and 78.9%, respectively. These effects of safflor yellow pigment increased with the increase of dose. . Because the thrombus material base formed on silk thread is platelet aggregation, the reduction of wet weight of thrombus is obviously the result of drug inhibition of platelet aggregation. It is consistent with the in vitro experiment that safflor yellow can inhibit ADP induced platelet aggregation. Safflower yellow can also significantly prolong the plasma recalcification time, prothrombin time and coagulation time in rabbits. It shows that it can affect the coagulation system in vivo and in vitro at the same time. In addition, safflower oil can reduce blood lipids.
2. effect on hypoxia tolerance of animals: 2.1. anti fatigue effect: compared with the control group (using the same amount of normal saline), the swimming time of safflower yellow 1100mg/kg mice was significantly prolonged, and the prolongation rate was 117.0%, p< 0.01.
2.2. effects on the tolerance of mice to normobaric hypoxia: mice with ipll00mg/kg safflor yellow pigment, compared with the control group (equal volume normal saline), after 30 minutes of administration, each mouse was put into a 125ml closed glass bottle containing 15g sodium lime, and the survival time of the experimental group was prolonged by 48.8%, P< 0.01.
2.3. effect on decompression and hypoxia tolerance of mice: after administration of the same method to mice for 30 minutes, the mice were put into a chamber with the same volume, sealed and decompressed to a negative pressure of 450mmHg, and observed for 60 minutes. , P< 0.001.
2.4. effect of increasing oxygen consumption by isoproterenol the experiment showed that safflower yellow could significantly prolong the survival time of mice to decompression and hypoxia (p< 0.001), but it did not significantly improve the survival rate.
2.5. effects on hypoxia of NaNO2 poisoned tissues: 10 mice in the experimental group and 10 mice in the control group were given safflor yellow 1100mg/kg for 30 minutes. Both groups of animals were given 0.1ml/10g of ip2%nano2 solution, and the survival time of mice was recorded. .
2.6. effects on cerebral ischemia and hypoxia: 24 mice were selected and divided into two groups. 30 minutes after IP safflor yellow 1100mg/kg, Yasuda's method of cerebral ischemia and hypoxia was used to slightly change. Observe the time from decapitation to the last gasp. The results showed that the duration of wheezing in the safflower yellow group (18.88 ± 4.02s) was significantly longer than that in the control group (12.83 ± 4.11s), and the prolongation rate was 47.2% (p< 0.01).
2.7. effects on myocardial hypoxia: safflower yellow can significantly increase the coronary flow of isolated rabbit heart and myocardial hypoxia. 0.2ml of 22% safflor yellow was injected into the perfused side tube, and the flow was recorded continuously for 1, 3, 5, 7, and 10 minutes. The mean value was taken, and the coronary flow before and after administration was compared. . Under nitrogen hypoxia, the coronary flow also increased significantly in 1-3 minutes (p< 0.01), and gradually decreased after 5 minutes. Safflower ethanol extract 4.0g/kg to rats IP and safflower Decoction 1.0g/kg to mice IP can significantly prolong the survival time under atmospheric hypoxia.
3. effect on uterus: Safflower decoction has excitatory effect on isolated uterus of mice, guinea pigs, rabbits and dogs. Anesthetized animal experiments showed that Decoction IV also had an excitatory effect on the eutopic uterus of mice, cats and dogs. No matter in vitro or after administration in the uterus, the tension or (and) rhythmicity increases significantly, and sometimes the excitatory effect is strong, which can cause spasticity. . Uterine fistula rabbits also showed uterine excitation reaction after IV decoction, the contraction frequency increased, the amplitude increased, and the effect was longer. It has also been reported that injection of safflower Decoction around the vagina of ovariectomized mice can significantly increase the weight of the uterus, suggesting an estrogen like effect.
4. analgesic and sedative effects: 40 mice were selected and divided into 4 groups. Respectively IP safflor yellow 550mg/kg, 1100mg/kg, morphine hydrochloride 20mg/kg and equal volume normal saline. . The writhing times of each mouse in 20 minutes were observed and compared with the control group, and the inhibition rate of mouse writhing response was calculated. Results two doses of safflor yellow could significantly inhibit the writhing reaction of mice, both P < 0.001. The mice in the above two dose groups were given IP barbital sodium subthreshold hypnotic dose of 300mg/kg or chloral hydrate subthreshold hypnotic dose of 250mg/kg after 30 minutes. The number of mice whose varus reflex disappeared for more than 1 minute in 30 minutes was observed, and the sleep rate of animals in each group was calculated. The results showed that the control animals given a subthreshold dose of barbital sodium were awake, and when combined with safflor yellow, the sleep rate increased by 40% at high dose and 70% at high dose (p< 0.01); The two doses can increase the falling asleep rate of subthreshold dose of chloral hydrate from 20% to 50% and 80% respectively (p< 0.01), suggesting that safflor yellow can significantly enhance the central inhibitory effect of barbital and chloral hydrate, and its effect is in parallel with the dosage.
5. anti inflammatory effect: 5.1. effect on formaldehyde induced paw swelling in rats: 15 rats were divided into three groups, ipll00mg/kg safflor yellow, hydrocortisone 20mg/kg and normal saline. Thirty minutes after administration, 0.05ml of sc2.5% formaldehyde solution on the left and right feet was used to induce inflammation. At 1, 3, 5, 7, and 24 hours after inflammation, the foot swelling thickness of rats was measured with a ruler, and compared with the foot swelling thickness before inflammation, and the foot swelling rate of each drug group at different times was calculated. . Thirty minutes later, histamine phosphate 50? g/0.05ml， Immediately ivl% Evans blue 10mg/kg. After 20 minutes, the animals were decapitated and sacrificed, and the skin was stripped. The blue stained area in the skin of the histamine injection site was observed and the difference between the two groups was compared. Results the staining areas of safflor yellow and control groups were 63.6 ± 9.9mm2 and 582.3 ± 6.6mm2 (x ± SD), respectively. The inhibition rate of the drug group was 89.1% (p< 0.001). It has obvious inhibitory effect on the increase of permeability of rat skin capillaries caused by histamine.
5.3. effect on the formation of cotton ball granuloma in rats: using the cotton ball method of Meier et al., one sterile cotton ball weighing 10mg was buried subcutaneously in both sides of the armpits of rats. Seven rats in the experimental group received ipll00mg/kg safflor yellow every day, while five rats in the control group received the same amount of normal saline for 4 days. The animals were sacrificed on day D5, and the cotton ball granulation tissue was removed, dried and weighed. The inhibition rate of granuloma formation was compared between the two groups. Results safflower yellow significantly inhibited the formation of cotton ball granuloma in rats (p< 0.001).
6. immune activity: Safflower polysaccharides are different from A-linked polysaccharides in higher plants, similar to polysaccharides of bacterial origin. The in vitro leaching experiment showed that safflower polysaccharide had synergistic effect with T cell mitogen ConA, but had no obvious effect on B cell mitogen DEX tcmlibansulfate. However, in vivo PFC test, safflower polysaccharide has the same trend with astragalus polysaccharide, which is generally believed to act on B cells. The change of PFC value of mice varies with the time of injection of safflower polysaccharide into mice: PFC in the administration group after sensitization is promoted, while PFC in the administration group before sensitization is inhibited. It showed that safflower polysaccharide also showed the bidirectionality of immune drugs. . Therefore, safflower polysaccharide can promote the transformation of lymphoid cells, increase the number of cells formed by splenocytes on sheep erythrocyte plaque, and resist the immunosuppressive effect of prednisolone, indicating that it is a new immunomodulator worthy of further study. In addition, safflower total Flavin (SY) decreased the content of serum lysozyme, the phagocytic function of peritoneal macrophages and whole blood leukocytes; Reduce PFC, SRFC and antibody production; In vitro, sy0.03-3.0, 0.1-2.o, and 0.1-2.5mg/ml inhibited TDR incorporated T and B lymphocyte transformation, MLC reaction, IL2 production, and its activity.
7. effects on nervous system: safflor yellow 0.55g/kg and 1.1g/kg in mice, and 0.3g/kg of pentobarbital sodium or 0.25g/kg of chloral hydrate in mice injected with a subthreshold dose of 0.3g/kg can improve the sleep rate (p< 0.01, p< 0.001), indicating that it can significantly enhance the central inhibitory effect of pentobarbital sodium and chloral hydrate, and its effect intensity is in parallel with the dosage. 1.1g/kg safflor yellow could significantly reduce the convulsion reaction rate and mortality of mice induced by Nikethamide (p< 0.05), but it could not resist pentylenetetrazol, caffeine and nitric acid? Base induced convulsions and death. Safflower injection 10g/kg, IP to Mongolian gerbils, can reduce the incidence of stroke caused by left carotid artery ligation on one side and significantly reduce cerebral edema caused by stroke, indicating that safflower may reduce the incidence of stroke and reduce cerebral edema. Because safflower can expand the branch circulation and increase the blood flow in the ischemic area of the brain, so as to reduce brain edema. Safflower can also reduce the metabolic disorder of monoamine neurotransmitters in brain tissue, and restore the decreased neurotransmitters to normal or close to normal. This may also be one of the mechanisms by which safflower reduces brain edema.