Research Progress on Chemical Constituents and Pharmacological Effects of Zhuang Medicine Cocculus laurifolius DC.

YongjingSU　AoXIE　HaichengWEN　WeiWEI

AbstractThis paper searched and summarized the relevant research literature on the chemical constituents and pharmacological effects of Cocculus laurifolius DC.， and provides a reference for further research on the quality standard of medicinal materials， clinical drug safety and the development and application of new drugs. The main chemical components of C. laurifolius are isoquinoline alkaloids. C. laurifolius has the pharmacological effects such as analgesic， hypotensive， antibacterial， free radical-scavenging activity， anticonvulsant， neuroprotective activity， anxiolytic and hypnotic effects.

Key wordsCocculus laurifolius; Chemical component; Alkaloid; Pharmacological effect

Cocculus laurifolius DC. is a herb of the Menispermaceae family whose whole plant or roots are used as a Zhuang medicine. It is mainly distributed in Guangxi， Guangdong， Yunnan， Hainan and other places. C. laurifolius is usually harvested in spring and winter. It is bitter in taste and slightly cold in nature. C. laurifolius is classified as a two-way medicine in Zhuang medicine， which has the functions of opening the dragon road， adjusting the water channel， dispelling wind and relieving pain and eliminating stasis to subdue swelling and is often used for treating rheumatism， low back pain， hypertension， edema and other diseases[1]. In order to promote the development and utilization of plant resources and the establishment of quality standards for the medicinal materials of C. laurifolius， this paper searched the relevant literature on the chemical constituents and pharmacological effects of C. laurifolius， and comprehensively summarized the research overview of the two aspects. This paper provides an important theoretical basis for the research on the quality standards of pharmaceutical materials， the safety of clinical medication and the development and application of new drugs.

Chemical Components

Isoquinoline alkaloids

Isoquinoline alkaloids are a class of alkaloids that are widely distributed in Papaveraceae， Menispermaceae， Ranunculaceae and other plants in a huge number. They have strong physiological activity， and their main pharmacological effects are anti-inflammatory[2]， antimalarial and antibacterial[3-4]， antiarrhythmic[5-7]， antihypertensive[8]， free radical-scavenging activity[9-10] and so on.

Zhang et al.[11] extracted C. laurifolius rhizomes with 85% ethanol and isolated coclaurine and used coclaurine hydrochloride to semi-synthesize Aconitum carmichaeli cardiotonic component D1-higenamine， opening up a new path for the production of this component.

Indian scholar Dewan S. Bhakuni[12] reviewed the extraction and isolation of 21 alkaloids from the roots， stems and leaves of C. laurifolius produced in India and Japan， namely cocculine， cocculidine， dihydroerysodine， NO-diacetyl derivative， isococculidine， isococculine， coccuvine， coccuvinine， cocculitine， cocculitinine， cocculidinone， cocculimine，  coccoline， coccolinine， coccudienone， sebiferine， stepharine， N-methylstepharine， laurifonine， laurifine， and laurifinine.

Dali M. Tsakadze[13]， a scholar in the Socialist Republic of Georgia， isolated 10 alkaloid components from the dried leaves of C. laurifolius， and collected 8 alkaloids from the leaves at the end of the flowering period in September： coculine （CHNO）， coculidine （CHNO）， coclafinin （CHNO）， cocclafin hy-drochloride （CHNOHCl）， coclaurune （CHNO）， isoboldine （CHNO）， norisoboldine （CHNO） and the new alkaloid coculidine N-oxide. They isolated and identified 2 alkaloids from leaves harvested in May： glaucine and talicmidine.

Zhang et al.[14] isolated two new bisbenzylisoquinoline alkaloids， α， α′-dioxo-7′-o-demethylstebisimine and 7′-o-demethylstebisimine and 14 known alkaloids from the roots of C. laurifolius and characterized them by pectroscopic methods. Japanese scholar Motoi Yogo[15] extracted and isolated a non-alkaloid component， coclauril， from the leaves of C. laurifolius， and clarified its structure by spectral analysis.

Japanese scholar Motoi Yogo[16] explored whether the composition of C. laurifolius leaf alkaloids has differences between producing areas with the purpose of checking the existence of abnormal type erythrinan， and found two new bases erythlaurine and erythramide. They also identified two known bases stepholidine and o-methylflavinantine.

Japanese scholars Inubushi  et al.[17] isolated a known non-phenolic alkaloid L-reticuline and a new alkaloid erythroculine from the leaves of C. laurifolius， and also isolated the known alkaloids laurifoline and magnoflorine from the water-soluble quaternary alkali fraction.

R. ziyaev[18] of the Republic of Uzbekistan extracted four alkaloids from the leaves of C. laurifoliu with chloroform， namely cocculine， isobolding， norisoboldine and a new alkaloid coclafine， and described their structures.

Other components

Indian scholar Alina paul[19] extracted and isolated 16 compounds from the leaves of C. laurifoliu using methanol solvent， namely neophytadiene， methylpalmitate， 4-nonenoic acid， methyl ester， t-phytol， stigmasterol， gamma-sitosterol， gamma-curcumene， methyl 8， 11， 14-eicosatrienoate， urs-12-ene， lupeol， ethyl iso-allocholate， squalene， longifolenaldehyde， （+-）-trans-1-isopropenyl-4-methyl-1， 4-cyclohexanediol， （-）-globuol， and dodecanedioic acid. And from the bark of C. laurifoliu， 23 compounds were extracted and isolated， namely coumaran， p-vinylguaiacol， pyrogallol dimethylether， neophytadiene， methyl palmitate， linoleic acid， methyl ester， 9-octadecenoic acid （Z）-， methyl ester， phytol， methyl stearate， myo-inositol， L-serine， ethyl ester， galactopyranoside， 3， 6， 9， 12， 15-pentaoxanonadecan-1-ol， butyraldehyde， semicarbazone， levoglucosan， alpha-1-rhamnopyranose， 5-methyl-2-hexanone oxime， n-isoamylacetamide， methyl pentofuranoside， inositol， 1-deoxy， glycerol beta-palmitate， 1， 2-enzenedicarboxylic acid， and methyl lignocerate. Most of these ingredients have anti-insect properties.

Pharmacological Action

Pain relief and blood pressure lowering

According to the Indian scholar Dewan S. Bhakuni[20]， cocculine and cocculidine were first isolated from the leaves of C. laurifolius. They have strong antibacterial activity， and magnoflorine， laurfoline， chlorides， o-methylisocorydine， isocorydine boldine， methochlorides appeared to inhibit the effect of d-tubocurarine on sciatica; and these quaternary bases induce hypotensive effects in dogs， cats and rabbits， and such activity is due to the considerable ganglionic blocking effect of these bases on various sympathetic and hypersympathetic ganglia.   Indian Dewan S. Bhakuni[17] isolated from the extract of the dried leaves of C. laurifolius with 50% ethanol， the main alkaloid isococculidine， which has hypotensive and neuromuscular blocking effects. Cocculidine and cocculine also have antihypertensive activity， which was found to be due to the ganglionic blocking effect on various sympathetic and parasympathetic ganglia， which is manifested in the effect similar to tubocurarine on sciatic nerves.

Antimicrobial and free radical scavenging activity

Pakistani scholar Muhammad Ajaib[21] extracted concentrated extracts from the leaves and bark of C. laurifolius using methanol， and tested the antimicrobial activity on 4 bacteria and 2 fungi. The results showed that both leaf and bark extracts had significant to average effects against bacteria and fungi， and the bark chloroform extract had significant DPPH free radical-scavenging activity.

Anticonvulsant and neuroprotective activity

Pakistani scholar Sidra Maqbool[22] evaluated the anticonvulsant and neuroprotective activity of ethanolic extract of C. laurifolius leaves on strychnine-induced convulsion in rats. The results showed that the ethanolic extracts （200 mg/kg and 400 mg/kg， p.o.） had significant anticonvulsant activity， manifested as delayed seizure onset and time to death after strychnine-induced convulsions. Meanwhile， the extracts had neuroprotective activity， which might be related to the antioxidant properties of the extracts， and acute toxicity tests did not show any toxic or neurotoxic side effects.

Antianxiety and hypnotic effects

Pakistani scholars Sidra Maqbool and Ishrat Younus[23] used the ethanol extract of C. laurifolius at two doses of 200 and 400 mg/kg in a mouse behavioral animal model （dark light experiment）， and the results demonstrated potential anxiolytic activity and minimal hypnotic activity at the higher dose of 400 mg/kg， while 200 mg/kg failed to produce hypnosis.

Pharmacognostical Study

The main report on the pharmacology of C. laurifolius is that Indian scholar Kishore S. Rajput[24] discovered the structure characteristics of young stems of C. laurifolius DC. in India， and conducted related research on the formation of continuous cambium and the structure of secondary xylem. Luo[25] identified the roots of C. laurifolius and Lindera aggregata （Sims） Kosterm.， and concluded that Lindera aggregata is spiny cone-shaped and has yellowish-brown surface， while the roots of C. laurifolius are harder and darker in color. The two are different in source， properties， efficacy， chemical composition and pharmacological effects.

Conclusions

The Zhuang medicine， C. laurifolius has a long history of medication in Guangxi ethnic areas. It is widely distributed， and its medicinal resources are easy to obtain. The research on the chemical components of C. laurifolius has found that it has anti-inflammatory， antimicrobial， antihypertensive， anti-anxiety and anticonvulsant and other active pharmacological ingredients， which have a variety of pharmacological effects， and are of great value for further in-depth research. Moreover， there have been no reports on the research on its pharmacology and quality standards at present. Therefore， further research is needed on the pharmacology， chemical composition and pharmacological effects of C. laurifolius to provide further reference for its clinical medicinal use.

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Editor： Yingzhi GUANG Proofreader： Xinxiu ZHU