Ligustrum lucidum – synergistic effects with other herbs and drugs in the management of cancer, bone marrow suppression, and depression?

I’ve written previously about the many medicinal properties of the dark red fruits of Ligustrum lucidum (Glossy Privet), the most invasive tree in New Zealand(1, 2). These include prophylactic effects against osteoporosis, beneficial effects on bone growth and strength, protection actions against liver toxins, and possible applications for one of our biggest and growing health burdens, diabetes mellitus.

During the March to June New Zealand Covid-19 Lockdown, I became more attentive to my local environment, and being a herbalist, plants featured prominently in this. Plants in our individual immediate environments can be useful as a source of food, recreation, exercise, de-stressing, and other survival related concerns, including as medicines.

It is however, a sad reflection on the current human disconnect from our local environment, that while this tree offers an evidence-based and readily available partial solution to common health problems experienced by thousands of New Zealanders, hardly anyone seems to know about this, or consider utilising this plant for something useful. Just as we viewed Mānuka many years ago, when it was cursed as an unwanted scrubweed by farmers, until its numerous medicinal properties became recognised again.

Ligustrum fruits are also used as an adjunct in cancer therapy(3). Inhibitory effects against benzopyrene and aflatoxin induced cancer(3, 4), potential applications in the treatment of liver(5) and brain(6) cancer, and enhanced sensitivity of human colorectal carcinoma cells to the chemotherapy drug doxorubicin(7), have been reported.

During chemotherapy treatment of cancer patients, a common and serious adverse event is myelosuppression, damage to the bone marrow resulting in decreased production of blood cells (haematopoiesis), and lowered immunity.

Ginseng (Panax ginseng) has been reported to ameliorate myelosuppression produced by the chemotherapy drug 5-flurouracil(8). Recent research now suggests that Ligustrum also may help with the clinical management of this condition, and that a combination of Ligustrum with Panax ginseng, even more so(9).

Mice who developed myelosuppression following administration of the chemotherapy drug cyclophosphamide, were given aqueous extracts of either Panax ginseng, Ligustrum lucidum, or a combination of these two herbs. Both ginseng and Ligustrum each individually increased levels and activity of several different haemotopoietic factors including peripheral blood cells, bone marrow cells and colony-forming unit-granulocyte macrophages, and upregulated cytokines involved in haematopoiesis. These protective effects against bone marrow suppression were even greater though, when a combination of Ginseng and Ligustrum was used.

Combining Ligustrum with Ginseng and using as an adjunctive treatment during chemotherapy treatment, may therefore help manage the negative effects on bone marrow thus enabling an optimal chemotherapy regimen to be implemented. Preventative effects against chemotherapy-induced myelosuppression have also been reported for a combination of Ligustrum with Eleutherococcus senticosus(10).

Other recent research on Ligustrum suggests it may also combine well with the highly regarded medicinal fungus Cordyceps(11). The Cordyceps genus are a type of fungi requiring an insect or insect larvae as host. Cordyceps has been used in TCM for over 300 years to treat a diverse range of conditions, including respiratory, kidney, liver and cardiovascular diseases, low libido, impotence, hyperlipidaemia, hyperglycaemia, fatigue, convalescence, and to promote energy(12).  Cordyceps is also gaining interest as a potential anti-cancer agent(13, 14), including as an inhibitor of metastases (secondary cancers), and as an adjunct during chemotherapy and radiotherapy(15, 16).

Unlike the closely related Cordyceps sinensis, a species restricted to a specific zone and insect host which has been overharvested in the wild and now endangered, Cordyceps militaris is cultivated on a range of host insects, and still contains significant levels of a key active compound cordycepin (3-deoxyadenosine). However, upon entering the body cordycepin is quickly metabolized into an inactive metabolite 3′-deoxyinosine, by the enzyme adenosine deaminase which is widely distributed in mammalian blood and tissues, thus limiting its activity when administered alone.

However, researchers in Shanghai have recently shown that oleanolic acid and ursolic acid, key triterpenoid constituents extracted from Ligustrum lucidum fruits, act as potent adenosine deaminase inhibitors. This suggests combining cordycepin or Cordyceps with Ligustrum, may be another useful combination in clinical practice(11).

Finally, potential applications of Ligustrum lucidum in the management of some types of depression, have recently been revealed(17).

Depression sometimes develops as a result of a head injury or in neurodegenerative disorders such as Parkinson’s disease or dementia, with central nervous system inflammation (neuroinflammation) being a common underlying factor. Recent clinical and preclinical evidence also suggests that this inflammation in nerve tissues may be a key factor involved in the onset of major depression(18).

Phenol glycosides from Ligustrum lucidum were evaluated for their effects on neuroinflammation and depressive-like behavior in mice. Mice received the Ligustrum derived extract for two weeks prior to treatment with lipopolysaccharide (LPS), which induced an inflammatory reaction. Ligustrum phenol glycoside pre-treatment ameliorated LPS-induced depressive-like behaviors, effects associated with reduced neuroinflammation of the hypothalamus, less activation of microglia (a type of brain cell) and inflammatory cytokine production, and improvement in vitamin D metabolism.

Like hundreds of other clever plants, Ligustrum lucidum has become so well colonised in New Zealand it is classed as a ‘noxious’ weed. The dark purple brown berries that appear in autumn make a wonderful healthy feast for our large bird population who excrete the seeds far and wide. And like lots of introduced plants endemic in our environment (weeds), it provides a readily accessible, free or cheap source of plant medicine with many potential benefits.

The above research on this plant is just some of that published this year to date. Perhaps assigning ‘shovel ready’ unemployed Kiwis to harvest the berries at the same time as culling numbers of this tree and undertaking further research towards processing these into natural medicines, might improve human and animal health, reduce medical care costs and prevent chronic debilitating illnesses. This would make sense in the Covid-19 plighted economy we are now living in.

 

Refs:

  1. Rasmussen PL, https://herbblurb.com/2016/03/10/ligustrum-lucidum-noxious-weed-or-useful-osteoporosis-treatment/
  2. Rasmussen PL, https://herbblurb.com/2019/01/24/honeysuckle-and-other-useful-weeds-surrounding-us/
  3. Wong BY et al, Mutat Res 1992; 279(3):209-216.
  4. Niikawa M et al, Mutat Res 1993; 319(1):1-9.
  5. Hu B et al, Oncol Rep 2014; 32(3):1037-1042.
  6. Jeong JC et al, Phytother Res 2011; 25(3):429-434.
  7. Zhang JF et al, Integr Cancer Ther 2011; 10(1):85-91.
  8. Raghavendran HRB et al, PLoS One. 2012;7(4):e33733.doi: 10.1371/journal.pone.0033733.
  9. Han J et al, J Ginseng Res. 2020 Mar;44(2):291-299.
  10. Wang C et al, Biomed Pharmacother 2019; 109:2062-2069.
  11. Guan H et al, Biomed Chromatogr. 2020 Mar;34(3):e4779
  12. Olatunju OJ et al, Fitoterapia 2018; 129; 293-316.
  13. Nakamura K et al, J Pharmacol Sci. 2015 Jan;127(1):53-6.
  14. Khan MA et al, Curr Med Chem.2020;27(6):983-996.
  15. Bi Y et al, Mol Pharm. 2018 Nov 5;15(11):4912-4925.doi:
  16. Ho SY et al, Int J Mol Sci. 2019 Oct 28;20(21):5366
  17. Feng R et al, Phytother Res. 2020 Jun 30.
  18. Troubat R et al, Eur J Neurosci 09 March 2020. 2020 Mar 9.doi: 10.1111/ejn.14720.

 

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