BioMed Research International

BioMed Research International / 2015 / Article
Special Issue

Chinese Medicine for Treating Endocrinology-Related Disease

View this Special Issue

Review Article | Open Access

Volume 2015 |Article ID 281873 |

Zunting Pang, Zhou Zhi-yan, Wei Wang, Yanni Ma, Niu Feng-ju, Xuelan Zhang, Chunchao Han, "The Advances in Research on the Pharmacological Effects of Fructus Ligustri Lucidi", BioMed Research International, vol. 2015, Article ID 281873, 5 pages, 2015.

The Advances in Research on the Pharmacological Effects of Fructus Ligustri Lucidi

Academic Editor: John E. Smith
Received10 Sep 2014
Accepted17 Nov 2014
Published22 Mar 2015


Fructus Ligustri Lucidi is a well-known invigorator in Chinese materia medica with hepatoprotective effect, anticancer activity, antioxidant activity, and so on. And oleanolic acids are the major pharmacologically active components in Fructus Ligustri Lucidi. So it has great value in medical health, and may be developed to a complementary and alternative medicine through further research. In this paper, the advances in research on pharmacological effects of Fructus Ligustri Lucidi were summarized by reviewing the recent related literature.

1. Introduction

Fructus Ligustri Lucidi (FLL, Nuzhenzi in Chinese) is the dried ripen fruit of Ligustrum lucidum Ait and it is a widely used herbal medicine for the prevention and treatment of a variety of pathologies. In the theory of Chinese traditional medicine, it has the effects of tonifying middle, calming five zang-organs, cultivating spirit, and nourishing the kidneys and liver. Besides, it can be applied to improve eyesight, replenish the liver and kidney, and promote the growth of black hair.

In recent decades, great progress about Fructus Ligustri Lucidi has been achieved by scholars inside and outside, and they have found a variety of active ingredients in Fructus Ligustri Lucidi, such as triterpenes, secoiridoid glucosides, volatile components, flavonoids, and phenolic compounds [1, 2]. In addition, modern pharmacological and chemical researches have indicated that Fructus Ligustri Lucidi has many pharmacological effects including hepatoprotective effect [35], anticancer activity [6, 7], antioxidant activity [810], immunomodulating effect [11], antiviral activity [12, 13], and antiosteoporosis activity [1423] (Table 1). Although the clinical researches about pharmacological effects of Fructus Ligustri Lucidi are less, Fructus Ligustri Lucidi as the alternative chemotherapeutic and chemopreventive agents have recently received more and more attention.

The pharmacological effectsActive compoundsReferences

Hepatoprotective effectOleanolic acid[35]
Anticancer activityAqueous extracts
Methanol extracts
[6, 7]
Antioxidant activitySecoiridoid glucosides
Hydroxytyrosol and salidroside
Ethanol extract
Immunomodulating effectOleanolic acid[11]
Antiviral activityOleanolic acid
Ursolic acid
[12, 13]
Antiosteoporosis activityEthanol extract
Water extracts

2. The Pharmacological Effects of Fructus Ligustri Lucidi

2.1. Hepatoprotective Effect

Oleanolic acid (OA, Figure 1) is a triterpenoid compound that exists widely in Fructus Ligustri Lucidi, and the hepatoprotective effect of OA was first reported in China and it has been used to treat liver disease in humans [3, 4]. Yim et al. have demonstrated that the fractions of chloroform and butanol derived from Fructus Ligustri Lucidi, which were enriched with oleanolic acid (OA), presented a dose-dependent protection against CCl4-induced hepatic injury in vivo. The promising hepatoprotective action may be associated with the enhancement of hepatic glutathione regeneration capacity (GRC), particularly under conditions of CCl4-induced oxidative stress [5].

2.2. Anticancer Activity

Liver cancer remains the fifth most common cancer in men and the seventh in women worldwide [24]. In China, traditional Chinese medicine (TCM) has a long history to treat liver cancer, and Fructus Ligustri Lucidi is known as the liver/kidney Yin tonifying herbs for liver cancer treatment [25]. Hu et al. have evaluated the effect of aqueous extracts of FFL on hepatocarcinoma cells, and significant apoptosis and cell senescence of hepatocellular carcinoma Bel-7402 cells by upregulating of p21 were observed [6].

On the other hand, because little information is available regarding the effect of FLL on glioma cell growth, Jeong et al. performed an experiment to investigate whether FLL extracts (extracted with methyl alcohol) affect glioma tumor growth. The results showed that glioma cell death could be caused by regulating the Akt/mTOR/survivin pathway in vitro [7].

2.3. Antioxidant Activity

Based on earlier reports, the human metabolic processes can produce harmful free radicals inevitably, which have been shown to possibly result in aging and other diseases [26, 27]. So, it is necessary to find effective radical scavengers in order to relieve the damaging effects of harmful free radicals.

Zhen-Dan he et al. have isolated ten secoiridoid glucosides from FLL by bioassay-guided analysis, and their effects on free radical induced by hemolysis of RBC were tested. And five of them ((1) oleoside dimethyl ester, (2) oleuropein, (3) neonuezhenide, (4) lucidumoside B, and (5) lucidumoside C, Figure 2) showed significant inhibitory effects on the hemolysis of red blood cells induced by free radicals [8]. Ju et al. extracted FLL five times with 50% ethanol, and the crude extract was partitioned with four-times-volume amounts of n-butanol, chloroform, and ethyl acetate. Then they performed a series of antioxidant experiments in vitro to evaluate the antioxidant and protective properties of the different fractions against H2O2-induced oxidative damage in SH-SY5Y cells. They demonstrated that the phenolic-enriched ethyl acetate (EtOAc) fraction, whose major components are hydroxytyrosol and salidroside, was the most active part in scavenging free radicals and increasing the levels of antioxidant enzymes [9].

In addition, Lin et al. examined the antioxidant activities of ethanol extract of Ligustrum lucidum fruits (ELL) and its pharmacological effects on BHT-induced oxidative stress in rats. In their study, compared to the BHT-treated group (1000 mg/kg), the significant decrease in the levels of sGOT, sGPT, BUN, sALP, Cr, TG, LDH, BALF LDH, and lipid peroxides in liver and lung and the enhancement in the levels of antioxidant enzymes in these organs in BHT-treated rats were observed in the ELL-treated groups (250, 500, and 1000 mg/kg), which supported the protective effect of ELL against BHT-induced oxidative stress [10].

2.4. Immunomodulating Effect

As mentioned above, OA is the main effective constituent of FLL. Because OA can stimulate Th1 cells leading to the secretion of Th1 cytokines and then upregulates the Th1/Th2 arms resulting in raising the percentage of CD4+CD8cells and promoting lymphocyte proliferation, OA has potential immunomodulatory effects. Wang et al. selected LLE as an immunoregulator, and they employed supercritical CO2 extraction technology to extract OA from FLL. Furthermore, immunomodulatory effect of OA on the immune cells of piglets was investigated through a series of experiments in vitro. Their results showed that OA, as an immunoadjuvant, has a beneficial and promising influence on the immune of piglets [11].

2.5. Antiviral Activity

It is well-known that hepatitis C virus (HCV) infection is a serious worldwide problem, which causes significant mortality and morbidity. Some reports have showed that HCV affects about 3% of the global population and approximately 20–30% have developed liver disease, such as liver cirrhosis and chronic hepatitis. To date, current therapy with adverse side effects has curative powers in about 50% of patients infected with HCV genotype 1 and many chronically infected patients remain untreated [2830]. So the progress of searching for effective antiviral drugs against HCV continues to be needed. And more and more researchers have studied the HCV inhibitors from FFL. Fortunately, accumulating evidence indicates that some active compounds of FLL were claimed to have potent antiviral activities against HCV. Lingbao Kong et al. found that oleanolic acid and ursolic acid (Figure 3) extracted from FLL are two antiviral components that possess anti-HCV activity based on their isomeric structures. They could suppress intracellular HCV NS5B RdRp activity. Moreover, they significantly inhibited the replication of HCV genotype 1b replicon and HCV genotype 2a JFH1 virus. By contrast, the results of their studies showed that oleanolic acid has one CH3 branched to last ring at C-20 position instead of C-19 position, so oleanolic acid had the better antiviral effect. In this way, the antiviral activity could be improved by modifying some compounds [12, 13].

2.6. Antiosteoporosis Activity

Fruit Ligustrum lucidum has long been used for the treatment of osteoporosis in China. Modern research in ovariectomized rats has demonstrated that the crude FLL extract could be useful to modulate the calcium balance and the turnover of bone [1416]. Some reports showed that the ethanol extract of FLL (EFLL) could directly enhance the mineralization process resulting in improving bone properties and calcium balance in aged female rats [1719]. These studies have provided evidence for the prevention and treatment of postmenopausal osteoporosis.

Ying Lyu et al. observed that FLL ethanol significantly increased bone mineral density and exerted beneficial improvement of bone mechanical properties in a dose-dependent manner by increasing Ca absorption and Ca retention, as well as reducing the RANKL/OPG ratio in growing female rats [20].

Estrogen deficiency and oxidative stress are considered as two major factors that cause the occurrence of osteoporosis [21, 22]. Thus, Chen et al. investigated the osteogenic constituents of FLL. They isolated and identified eight compounds from the aqueous extract of FLL (AFLL), namely, tyrosol (1), tyrosyl acetate (2), salidroside (3), hydroxytyrosol (4), oleoside dimethyl ester (5), nuzhenide (6), oleoside-7-ethyl-11-methyl ester (7), and G13 (8). Further studies showed that all eight compounds exhibited the antiosteoporotic effect with different mechanisms such as antioxidative effects and ER-dependent or independent pathways [23].

3. Conclusion

Fructus Ligustri Lucidi (FLL, Chinese name, Nuzhenzi) has been used in traditional Chinese medicine for over 1000 years. It contains a number of bioactive components. Moreover, FLL has been known to have hepatoprotective effect, anticancer activity, antioxidant activity, immunomodulating effect, antiviral activity, and antiosteoporosis activity, and other pharmacodynamic effects have been demonstrated as well, such as the treatment of coronary heart disease [31]. The chemical constituents of FLL include polysaccharides, triterpenes, secoiridoids, and flavonoids, which may be contributed to the pharmacological activities of FLL [3234]. Therefore, the pharmacological effects and health function of Fructus Ligustri Lucidi are more and more focused on in the world.

Conflict of Interests

The authors declare that there is no conflict of interests.


This work was supported by the Foundation of Jinan Science and Technology Development Program (201303055). This project was supported by Project of Shandong Province Higher Educational Science and Technology Program (J14LK61). This project was also supported by National Natural Science Foundation of China (81373968).


  1. Z.-D. He, H. Dong, H.-X. Xu, W.-C. Ye, H.-D. Sun, and P. P.-H. But, “Secoiridoid constituents from the fruits of Ligustrum lucidum,” Phytochemistry, vol. 56, no. 4, pp. 327–330, 2001. View at: Publisher Site | Google Scholar
  2. Z.-D. He, S. Ueda, M. Akaji, T. Fujita, K. Inoue, and C.-R. Yang, “Monoterpenoid and phenylethanoid glycosides from Ligustrum pedunculare,” Phytochemistry, vol. 36, no. 3, pp. 709–716, 1994. View at: Publisher Site | Google Scholar
  3. B. Wang and Z. Jiang, “Studies on oleanolic acid,” Chinese Pharmaceutical Journal, vol. 17, no. 27, pp. 393–397, 1992. View at: Google Scholar
  4. W. F. Pak, “Therepeutic efficacy of oleanolic acid on acute jaundice hepatitis and histology of experiment animals,” Bulletin Chinese Traditional Herb Drugs, vol. 17, no. 4, pp. 32–36, 1977. View at: Google Scholar
  5. T. K. Yim, W. K. Wu, W. F. Pak, and K. M. Ko, “Hepatoprotective action of an oleanolic acid-enriched extract of Ligustrum lucidum fruits is mediated through an enhancement on hepatic glutathione regeneration capacity in mice,” Phytotherapy Research, vol. 15, no. 7, pp. 589–592, 2001. View at: Publisher Site | Google Scholar
  6. B. Hu, Q. Du, S. Deng et al., “Ligustrum lucidum Ait. fruit extract induces apoptosis and cell senescence in human hepatocellular carcinoma cells through upregulation of p21,” Oncology Reports, vol. 32, no. 3, pp. 1037–1042, 2014. View at: Google Scholar
  7. J. C. Jeong, J. W. Kim, C. H. Kwon, T. H. Kim, and Y. K. Kim, “Fructus ligustri lucidi extracts induce human glioma cell death through regulation of Akt/mTOR pathway in vitro and reduce glioma tumor growth in U87MG xenograft mouse mode,” Phytotherapy Research, vol. 25, no. 3, pp. 429–434, 2011. View at: Publisher Site | Google Scholar
  8. Z.-D. He, P. P.-H. But, T.-W. D. Chan et al., “Antioxidative glucosides from the fruits of Ligustrum lucidum,” Chemical and Pharmaceutical Bulletin, vol. 49, no. 6, pp. 780–784, 2001. View at: Publisher Site | Google Scholar
  9. H.-Y. Ju, S. C. Chen, K.-J. Wu et al., “Antioxidant phenolic profile from ethyl acetate fraction of Fructus Ligustri Lucidi with protection against hydrogen peroxide-induced oxidative damage in SH-SY5Y cells,” Food and Chemical Toxicology, vol. 50, no. 3-4, pp. 492–502, 2012. View at: Publisher Site | Google Scholar
  10. H. M. Lin, F. L. Yen, L. T. Ng, and C. C. Lin, “Protective effects of Ligustrum lucidum fruit extract on acute butylated hydroxytoluene-induced oxidative stress in rats,” Journal of Ethnopharmacology, vol. 111, no. 1, pp. 129–136, 2007. View at: Publisher Site | Google Scholar
  11. J. Wang, A. Shan, T. Liu, C. Zhang, and Z. Zhang, “In vitro immunomodulatory effects of an oleanolic acid-enriched extract of Ligustrum lucidum fruit (Ligustrum lucidum supercritical CO2 extract) on piglet immunocytes,” International Immunopharmacology, vol. 14, no. 4, pp. 758–763, 2012. View at: Publisher Site | Google Scholar
  12. L. Kong, S. Li, X. Han et al., “Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from Fructus Ligustri Lucidi,” Virus Research, vol. 128, no. 1-2, pp. 9–17, 2007. View at: Publisher Site | Google Scholar
  13. L. Kong, S. Li, Q. Liao et al., “Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity,” Antiviral Research, vol. 98, no. 1, pp. 44–53, 2013. View at: Publisher Site | Google Scholar
  14. Y. Zhang, W.-P. Lai, P.-C. Leung, C.-F. Wu, X.-S. Yao, and M.-S. Wong, “Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats,” Biological and Pharmaceutical Bulletin, vol. 29, no. 2, pp. 291–296, 2006. View at: Publisher Site | Google Scholar
  15. Y. Zhang, W.-P. Lai, P.-C. Leung, C.-T. Che, and M.-S. Wong, “Improvement of Ca balance by Fructus Ligustri Lucidi extract in aged female rats,” Osteoporosis International, vol. 19, no. 2, pp. 235–242, 2008. View at: Publisher Site | Google Scholar
  16. X.-L. Dong, M. Zhao, K.-K. Wong, C.-T. Che, and M.-S. Wong, “Improvement of calcium balance by Fructus Ligustri Lucidi extract in mature female rats was associated with the induction of serum parathyroid hormone levels,” British Journal of Nutrition, vol. 108, no. 1, pp. 92–101, 2012. View at: Publisher Site | Google Scholar
  17. Y. Zhang, P.-C. Leung, C.-T. Che, H.-K. Chow, C.-F. Wu, and M.-S. Wong, “Improvement of bone properties and enhancement of mineralization by ethanol extract of Fructus Ligustri Lucidi,” British Journal of Nutrition, vol. 99, no. 3, pp. 494–502, 2008. View at: Publisher Site | Google Scholar
  18. C. H. Ko, W. S. Siu, C. P. Lau, C. B. S. Lau, K. P. Fung, and P. C. Leung, “Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats,” Chinese Medicine, vol. 5, article 39, 2010. View at: Publisher Site | Google Scholar
  19. G. Li, X.-A. Zhang, J.-F. Zhang et al., “Ethanol extract of Fructus Ligustri Lucidi promotes osteogenesis of mesenchymal stem cells,” Phytotherapy Research, vol. 24, no. 4, pp. 571–576, 2010. View at: Publisher Site | Google Scholar
  20. Y. Lyu, X. Feng, P. Zhao et al., “Fructus Ligustri Lucidi (FLL) ethanol extract increases bone mineral density and improves bone properties in growing female rats,” Journal of Bone and Mineral Metabolism, vol. 32, no. 6, pp. 616–626, 2014. View at: Publisher Site | Google Scholar
  21. Q. Chen, L. Yang, G. Zhang, and F. Wang, “Bioactivity-guided isolation of antiosteoporotic compounds from Ligustrum lucidum,” Phytotherapy Research, vol. 27, no. 7, pp. 973–979, 2013. View at: Publisher Site | Google Scholar
  22. R. Pacifici, “Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis,” Journal of Bone and Mineral Research, vol. 11, no. 8, pp. 1043–1051, 1996. View at: Google Scholar
  23. M. Abdollahi, B. Larijani, R. Rahimi, and P. Salari, “Role of oxidative stress in osteoporosis,” Therapy, vol. 2, no. 5, pp. 787–796, 2005. View at: Publisher Site | Google Scholar
  24. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA: A Cancer Journal for Clinicians, vol. 61, no. 2, pp. 69–90, 2011. View at: Publisher Site | Google Scholar
  25. X. Bo, X. M. Zhao, H. T. Liu, W. G. Ma, and H. Li, “A study on 4 kinds of Chinese medicines reducing arrest of bone marrow by cyclophosphomidum,” Journal of the Beijing Union University (Natural Science), vol. 17, no. 8, pp. 58–61, 1994. View at: Google Scholar
  26. B. Halliwell and J. M. C. Gutteridge, Free Radicals in Biology and Medicine, Oxford University Press, Oxford, UK, 1999.
  27. M. E. J. Lean, M. Noroozi, I. Kelly et al., “Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA,” Diabetes, vol. 48, no. 1, pp. 176–181, 1999. View at: Publisher Site | Google Scholar
  28. P. P. Ip, H. W. Nijman, J. Wilschut, and T. Daemen, “Therapeutic vaccination against chronic hepatitis C virus infection,” Antiviral Research, vol. 96, no. 1, pp. 36–50, 2012. View at: Publisher Site | Google Scholar
  29. T. J. Liang, B. Rehermann, L. B. Seeff, and J. H. Hoofnagle, “Pathogenesis, natural history, treatment, and prevention of hepatitis C,” Annals of Internal Medicine, vol. 132, no. 4, pp. 296–305, 2000. View at: Publisher Site | Google Scholar
  30. V. de Re, “Interferon-based therapy for chronic hepatitis C: current and future perspectives,” Hepatitis Monthly, vol. 10, no. 3, pp. 231–232, 2010. View at: Google Scholar
  31. M. L. Li, “Progress in the study on Fructus Ligustri Lucidi,” Zhongguo Zhong and Yao Za Zhi, vol. 19, no. 8, pp. 504–506, 1994 (Chinese). View at: Google Scholar
  32. X. H. Xu, N. Y. Yang, S. H. Qian, N. Xie, M. Y. Yu, and J. A. Duan, “Study on flavonoids in Ligustrum lucidum,” Journal of Chinese Medicinal Materials, vol. 30, no. 2, pp. 538–540, 2007. View at: Google Scholar
  33. X.-H. Xu, N.-Y. Yang, S.-H. Qian, N. Xie, and J.-A. Duan, “Dammarane triterpenes from Ligustrum lucidum,” Journal of Asian Natural Products Research, vol. 10, no. 1, pp. 33–37, 2008. View at: Publisher Site | Google Scholar
  34. S. Aoki, Y. Honda, T. Kikuchi et al., “Six new secoiridoids from the dried fruits of Ligustrum lucidum,” Chemical and Pharmaceutical Bulletin, vol. 60, no. 2, pp. 251–256, 2012. View at: Publisher Site | Google Scholar

Copyright © 2015 Zunting Pang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly as possible. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Review articles are excluded from this waiver policy. Sign up here as a reviewer to help fast-track new submissions.