1、 Asarum pharmacopoeia standard
This product is the dried roots and rhizomes of Asarum heterotropoides fr. Schmidt var.mandshuricum (maxim.) kitag., Asarum sieboldii miq.var.seoulense Nakai or Asarum sieboldii miq. of the Aristolochiaceae family. The first two are commonly known as "Asarum sibiricum". Excavate in summer or early autumn to remove the aboveground part and sediment and dry in the shade.
[character] Asarum heterophyllum often curls into clusters. The rhizome is transversely irregular cylindrical, with short branches, 1-10cm long and 0.2-0.4cm in diameter; the surface is grayish brown, rough, with annular nodes, 0.2-0.3cm long internodes, and bowl shaped stem marks on the top of branches. The root is slender, on dense nodes, 10-20cm long, 0.1cm in diameter; the surface is grayish yellow, smooth or with longitudinal wrinkles; There are fibrous roots and fibrous root scars; It is brittle, easy to break, with flat section, yellowish white or white. .
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The rhizome of Asarum heterophyllum is 5 ～ 20cm long, 0.1 ～ 0.2cm in diameter, and 0.2 ～ 1cm in internode length. The odor is weak.
. The cortex is wide, with numerous oil cells scattered; 1 row of cells in the outer cortex, oblong like, corky and slightly lignified; The endothelial layer is obvious, and the Kjeldahl point can be seen. There are 1-2 layers of columella cells and 2-4 prototypes of primary xylem. In the center of the phloem bundle, there are 1-3 parenchymal cells significantly larger than the surrounding phloem cells, but their length and diameter are significantly smaller than the maximum vessel diameter, or there are no obvious large parenchymal cells in the phloem. Parenchyma cells contain starch granules.
(2) Take 0.5g of this product powder, add 20ml of methanol, sonicate for 45 minutes, filter, evaporate the filtrate, add 2ml of methanol to dissolve the residue, and use it as the test solution. Take 0.5g of Asarum reference medicine, and make the reference medicine solution in the same way. Then take asaronin reference substance and add methanol to make a solution containing 1mg per 1ml as the reference solution. According to the test of thin-layer chromatography (general rule 0502), suck 10 μ l each of the above three solutions, dot them on the same silica gel G thin-layer plate, use petroleum ether (60 ～ 90 ℃) - ethyl acetate (3:1) as the developing agent, develop, take out, dry, spray 1% vanillin sulfuric acid solution, and blow hot air until the spots are clear. In the chromatogram of the test sample, spots with the same color appear at the corresponding positions of the chromatogram of the control medicinal material and the chromatogram of the control sample.
[inspection] the moisture content shall not exceed 10.0% (the third method of general rule 0832).
The total ash content shall not exceed 12.0% (general rule 2302).
Acid insoluble ash content shall not exceed 5.0% (general rule 2302).
Aristolochic acid I was determined by HPLC (general rule 0512).
Chromatographic conditions and system suitability test octadecylsilane bonded silica gel was used as filler; Acetonitrile was used as mobile phase a, and 0.05% phosphoric acid solution was used as mobile phase B. gradient elution was performed according to the following table; The detection wavelength was 260nm. The number of theoretical plates should not be less than 5000 according to aristolochic acid I peak.
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Time (min) mobile phase a (%) mobile phase B (%)
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0～10 30→34 70→66
10～18 34→35 66→65
18～20 35→45 65→55
20～30 45 55
30～31 45→53 55→47
31～35 53 47
35～40 53→100 47→0
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Preparation of reference solution take an appropriate amount of aristolochic acid I reference substance, weigh accurately, add methanol to make a solution containing 0.2 μ g per 1ml.
Preparation of test solution take about 0.5g of powder in this product, weigh accurately, place in a corked conical flask, add 25ml of 70% methanol precisely, close the stopper, weigh, sonicate (power 500W, frequency 40KHz) for 40 minutes, cool, weigh again, make up the lost weight with 70% methanol, shake well, filter, and take the filtrate.
The determination method is to precisely suck 10 μ l of the reference solution and 10 μ l of the test solution, inject them into the liquid chromatograph, and determine.
The content of aristolochic acid I (c17h11no7) in this product shall not exceed 0.001% when calculated as a dry product.
[extract] according to the hot leaching method under the determination method of alcohol soluble extract (general rule 2201), the use of ethanol as solvent shall not be less than 9.0%.
[content determination] the volatile oil shall be determined according to the volatile oil determination method (general rule 2204).
The volatile oil content of this product shall not be less than 2.0% (ml/g).
Asaronin was determined by HPLC (general rule 0512).
Chromatographic conditions and system suitability test octadecylsilane bonded silica gel was used as filler; Use acetonitrile as mobile phase A and water as mobile phase B to perform gradient elution according to the following table; The column temperature was 40 ℃, and the detection wavelength was 287nm. The number of theoretical plates should not be less than 10000 according to the asarin peak.
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Time (min) mobile phase a (%) mobile phase B (%)
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0～20 50 50
20～26 50→100 50→0
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Preparation of reference solution take an appropriate amount of asaronin reference substance, weigh accurately, add methanol to make a solution containing 50 μ g per 1ml.
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The determination method is to precisely suck 10 μ l of the reference solution and 10 μ l of the test solution, inject them into the liquid chromatograph, and determine.
According to the calculation of dry product, the content of asaronin (c20h18o6) shall not be less than 0.050%.
Decoction pieces
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This product has irregular sections. The rhizome is irregular and round, and its outer skin is gray brown, and sometimes circular nodes can be seen. The root is thin, the surface is grayish yellow, smooth or with longitudinal wrinkles. The cut surface is yellowish white or white. .
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[identification] (except for the root cross section) [inspection] (aristolochic acid I limit) [extract] [content determination] is the same as that of medicinal materials.
[nature, taste and meridian tropism] pungent, warm. Return to heart, lung and kidney meridians.
[functions and indications] relieve exterior cold, dispel wind and relieve pain, dredge the orifices, warm the lungs and turn the drink into liquid. It is used for cold, headache, toothache, nasal congestion, runny nose, epistaxis, rhinorrhea, rheumatic arthralgia, phlegm and cough.
[usage and dosage] 1 ～ 3G. Take 0.5 ～ 1g of the powder each time. Use appropriate amount externally.
[note] it should not be used with resveratrol.
[storage] store in a cool and dry place.

2、 Chemical constituents of Asarum

1. the whole herb (dry product) of Asarum heterophyllum (produced in Liaoning) contains 2.5% of volatile oil. The components of volatile oil include: a-pinene, camphene, β - pinene, myrcene, sabinene, limonene, 1,8-cineole, p-cymene, y-terpinene, terpinolene,Borneol（borneol）， Eucarvone, estcmlibagole, 2-isopropyl-5-methylanisole, 3,5-dimethoxytoluene, safrole, methyl eugenol,Alpha asarone，Myristicate ether（myristicin），ElemeneElemicin, β - phellanrene, β - Terpinene, 3,4-dimethyl-2,4,6-octatcmlibiene, epicarp, isoborneol, a-terpineol, pen tadecane, β - bisabelene, 2-methoxysafrole,Carcumol(kakuol), n-isobutyldodecatetcmlibaeneamide. It also contains hi genamine.
2. the whole herb (dry product) of Asarum heterophyllum (produced in Hubei) contains 2.6% of the volatile oil. The components of the volatile oil include: a-pinene, camphene, β -pinene, myrcene, sabinene, limonene, 1,8-cineole, p-cymine, γ -terpinene, ter[omp; EME),Borneol（borneol）， Terpinen-4-ol, a-terpineol, estcmlibagole, naphthalene, 3,5-dimethoxytoluene, safrole, n-Pentadecane, methyleugenol, 2-methoxysafrole,Alpha asarone，Myristicate ether（myristicin）， Elemicin, a-thujene,Asaronin（asarinin）。
3. Asarum Hancheng (Liaoning) whole grass (dry product) contains 1.0% volatile oil. In addition to methyleugenol, safrole, asaricin and Eucarvone, the volatile oil also contains a-pinene, camphene, β - pinene, myrcene, sabinene, limonene, l, 8-cineole, p-cymene,BorneolBorneol, a-terpieol, p-cymen-a-ol, estcmlibagole, 2-isopropyl-5-methylanisole,Borneol acetate（bornyl acetate）, 3,5-dimethoxytoluene, myristicin and elemicin, etc.

3、 Pharmacological action of Asarum

. A.h.0.1-0.4ml/kg was injected intravenously in cardiopulmonary preparation dogs. The results showed that LVSP ↑, LVEDP ↓, map ↑, Co ↑, HR ↑, SV ↓, dp/dtmax ↑, -dp/dtmax ↑, t-dp/dtmax ↓, VPM ↑, VCE CPIP ↑, Vmax ↑; In anesthetized open chest dogs, intravenous injection of 0.05-0.4ml/kga.h can make map ↓ and SV ↑, and other results are basically consistent with cardiopulmonary preparation experiments; The positive anterior descending branch of the LIS sajous figure measured in the above two experiments shifted to the upper right. Thus excluding the influence of pre and post load, it shows that the improvement of pump function seems to be caused by the enhancement of myocardial contractility by A.H. A. H and DL noraconitine (abbreviated as H.G) and isoproterenol (abbreviated as i.s) contained in Asarum heterophyllum were compared. Results all three can enhance left ventricular function, but A.H can increase SV, H.G and i.s can reduce SV. The reason may be related to the moderate increase of heart rate and complete ventricular relaxation caused by A.H.
1.2. effect of Asarum on cardiogenic shock in dogs: the root of Asarum heterotcmliboids was used to make a 1:2 aqueous solution. A canine model of cardiogenic shock was established by segmented ligation of the anterior descending branch of the coronary artery and coronary sinus cutting blockage. Results Asarum extract dopamine and asarum effective component noraconitine can both increase map, LVSP, ± lvdp/dtmax and SCBF, and reduce CVR in shock animals. The effects of dopamine and asarum extract are similar, but dopamine accelerates heart rate while Asarum does not.

2. effects on the central nervous system: 2.1. synergistic effects of central inhibitory drugs: 50mg/kg of methyleugenol contained in the volatile oil of this product was injected intraperitoneally into mice, and 15mg/kg of sodium pentobarbital at a subthreshold dose was injected intraperitoneally 20 minutes after administration. Results all mice in the administration group fell asleep, p< compared with the control; 01, which significantly synergized with the hypnotic effect of pentobarbital sodium. Intraperitoneal injection of methyleugenol 50mg/kg and 100mg/kg in mice could significantly prolong the sleep time of thiopental sodium (dose of intravenous injection, 25mg/kg), P< 0.01. The central inhibitory effect of chlorpromazine (15mg/kg) was significantly enhanced by intraperitoneal injection of methyl eugenol 144mg/kg in rats, P< 0.01.

2.2. anesthetic effect on animals of different species: methyleugenol is administered to animals of different species at a rate of 2.0ml (50mg/ml) per minute. Generally, it enters anesthesia 1-2 minutes after intravenous injection. When the dose of 50mg/kg was injected intravenously into cats, salivary secretion increased significantly and neck ankylosis occurred; Digestive tract reactions such as vomiting and defecation occurred in dogs after administration; However, monkeys and rabbits have basically no such reactions after administration, but if the administration is too fast, the breathing may slow down or even stop, and if the drug is stopped immediately, the breathing can recover.

2.3. analgesic effect: methyl eugenol has certain analgesic effect on mice, but the specificity is not high. Asarum decoction can block the impulse conduction of toad sciatic nerve with reversibility.

2.4. cooling effect: methyleugenol has obvious cooling effect on rats by intraperitoneal injection of 90mg/kg and 144mg/kg, but it is weaker than chlorpromazine (15mg/kg).

3. effects on EEG activity in rabbits: the synchronous recording of Asarum volatile oil on the cerebral cortex, hippocampus, mesencephalic reticular formation and ECG of rabbits proves that its effect on the center is similar to that of barbiturates, with a development process of desynchronization low amplitude fast wave → high amplitude slow wave → low amplitude slow wave → intermittent EEG loss → EEG continuous disappearance. The disappearance of ECG occurred after the disappearance of EEG in cortex, hippocampus and midbrain reticular formation.

4. effect on microcirculation: the mouse model of Auricle Microcirculation Disorder was induced by epinephrine. First measure and record the pipe diameter and blood flow before administration, and then intraperitoneal injection of Asarum 0.1ml/10g according to body weight to observe the changes of pipe diameter and blood flow within 10 minutes, and then intraperitoneal injection of epinephrine 10 μ g/10g body weight to observe the changes of blood flow and pipe diameter within 10 minutes. The experimental results showed that Asarum had a delayed effect on the arrest or slowing down of microarterial blood flow caused by mild epinephrine, but the statistical treatment was not significant.

5. anti inflammatory effect: the volatile oil extracted from Asarum heterophyllum (Asarum heterophyllum oil for short) was intraperitoneally injected into rats at a dose of 0.24ml/kg, which had an inhibitory effect on rat foot swelling caused by carrageenan. Compared with the control group, P< 0.001. This effect also existed in adrenalectomized rats, similar to the effect of cortisone acetate 40mg/kg. Asarum oil can reduce the histamine content in tissues and exudates of inflammatory rats, but the contents of 5-HT and PGE2 have no significant difference from the control group. It has an inhibitory effect on the rat foot swelling caused by histamine or PGE2, but has no inhibitory effect on the foot swelling caused by 5-HT. Asarum oil can also resist the increase of capillary permeability caused by histamine or PGE2; It can inhibit the white blood cell migration caused by carrageenan injection in the thoracic cavity of rats; .

6. bacteriostatic effect: the preliminary in vitro test showed that Asarum has some inhibitory effects on hemolytic streptococcus, Shigella, typhoid bacillus and Mycobacterium tuberculosis. .

. Noraconitine is contained in attachment 3, asarum, Evodia rutaecarpa and other cold dispelling drugs, and its pharmacological effect conforms to the pharmacological basis of cold dispelling drugs.

8. antihistamine and anti-inflammatory reaction: methylsyringol, hakucl, n-isobutyl dodecyl tetraeneamine and noraconitine obtained from Asarum heterophyllum can significantly inhibit the contraction of isolated ileum of guinea pigs made of histamine. The water or ethanol extract of Asarum can reduce the total release of allergic mediators in rapid allergic reaction by more than 40%. .

9. effect on smooth muscle: Asarum volatile oil on rabbit uterus and intestine in vitro, low concentration makes the tension first increase and then decrease, and the amplitude increases; At high concentration, it was inhibited. It has inhibitory effect on isolated rat uterus.

10. effects on respiratory system: Huaxi octanol infusion intravenously injected in rabbits can resist the respiratory depression caused by morphine. Methylsyringol has a significant relaxing effect on isolated guinea pig trachea. The pulmonary perfusion volume of the isolated lung was first transiently decreased and then continued to increase, which could last for 15-30 minutes. Isoproterenol did not first decrease transiently, but the increase and duration of pulmonary perfusion volume were similar to those of Asarum. Therefore, it is believed that the subsequent effect of Asarum is similar to that of isoproterenol.