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JKM > Volume 43(1); 2022 > Article
Kim and Chong: The Anti-depressive Effect of Rehmanniae Radix Preparata via Anti-inflammatory Activity

Abstract

Objectives

Rehmanniae Radix Preparata (RRP) has been used as a traditional remedy to treat gynecology and endocrine diseases. Recently, studies on antioxidant and anti-inflammatory effects of RRP have been reported, so it was judged that RRP extracts would have an anti-depressive effect.

Methods

We investigated the anti-neuroinflammatory and anti-depressive effect of RRP on lipopolysaccharide (LPS)-induced depression and LPS-stimulated BV2 microglia. RRP inhibited the LPS-stimulated excessive release of nitrite in the BV2 cells. RRP also significantly inhibited the inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated BV2 microglial cells.

Results

RRP significantly suppressed the LPS-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-κB activation. In addition, administration of RRP not only inhibited the immobility time in the forced swimming test (FST) but also increased the total travel distance in the open field test (OFT). Also, RRP inhibited the elevation of TNF-alpha, IL-1beta, and IL-6 in brain of LPS-injected mice.

Conclusions

Considering the overall results, our study showed that RRP exhibited the anti-neuroinflammatory and anti-depressive activities via deactivation of MAPKs and NF-κB.

Fig. 1
Effect of RRP on cell viability in BV2 cells.
Cells were treated with saline or the RRP (0.1, 0.2, 0.5, 1, and 2 mg/mL) for 24 h. Cell viability was determined by MTT assay, as described in Methods. Data are the mean ± S.D.(n = 3). *p < 0.05 versus the saline. RRP: Rehmanniae Radix Preparata.
jkm-43-1-99f1.gif
Fig. 2
Effect of RRP on LPS-induced nitrite production in BV2 cells.
BV2 cells were incubated with saline, RRP(0.1, 0.2, and 0.5 mg/mL) or FXT(Fluoxetine 10 μM), and then stimulated with 1 μg/mL of LPS for 24 h. The concentrations of nitrite were determined by Griess reagent, as described in methods. Data are the mean ± S.D.(n = 3). *p < 0.05 versus the saline, p < 0.05 versus LPS. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f2.gif
Fig. 3
Effect of RRP on inflammatory cytokine expression in LPS-stimulated BV2 cells.
Cells were pre-treated with saline or RRP(0.1, 0.2, and 0.5 mg/mL) or FXT(Fluoxetine 10 μM) for 1 h and then stimulated with 1 μg/mL of LPS for 24 h. The mRNA expression level of IL-1β, IL-6, TNF-α were measured by qPCR. Data are the mean ± S.D.(n = 3). *p < 0.05 versus saline, p < 0.05 versus LPS. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f3.gif
Fig. 4
Effect of RRP on the activation of MAPKs and the degradation of Iκ-Bα in LPS-stimulated BV2 cells.
Cells were treated with the saline or RRP(0.5 mg/mL) for 1 h, and then stimulated with 1 μg/mL of LPS for 30 min. The protein expressions were measured by western blot. The experiment was repeated three times, and similar results were obtained. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f4.gif
Fig. 5
Effect of RRP on Force swimming test (FST) in the LPS-induced depressive-like behavior.
Data are the mean ± S.D.(n = 3). *p < 0.05 versus saline, p < 0.05 versus LPS. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f5.gif
Fig. 6
Effect of RRP on Open field test (OFT) in the LPS-induced depressive-like behavior.
Data are the mean ± S.D.(n = 3). *p < 0.05 versus saline, p < 0.05 versus LPS. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f6.gif
Fig. 7
Effect of RRP on inflammatory cytokines in the LPS-induced depressive-like model.
The mRNA expression level of IL-1β, IL-6, TNF-α were measured by qPCR. Data are the mean ± S.D.(n = 3). *p< 0.05 versus saline, p < 0.05 versus LPS. RRP: Rehmanniae Radix Preparata, FXT: Fluoxetine.
jkm-43-1-99f7.gif
Table 1
The Primer of IL-1β, IL-6, TNF-α, GAPDH
Gene Primer
IL-1β 5′-CCT CGT GCT GTC GGA CCC AT-3′(forward)
5′-CAG GCT TGT GCT CTG CTT GTG A-3′(reverse)

IL-6 5′-CCG GAG AGG AGA CTT CAC AG-3′(forward)
5′-CAG AAT TGC CAT TGC ACA AC-3′(reverse)

TNF-α 5′-GTG GAA CTG GCA GAA GAG GC-3′(forward)
5′-AGA CAG AAG AGC GTG GTG GC-3′(reverse)

GAPDH 5′-TGT GTC CGT CGT GGA TCT GA-3′(forward)
5′-TTG CTG TTG AAG TCG CAG GAG-3′(reverse)

참고문헌

1. WHO. Pharmacological treatment of mental disorders in primary health care. Geneva: World Health Organization;2009.


2. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR. 2003; The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 289:3095–3105.
crossref pmid

3. Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA. 2003; The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 64:1465–1475.
crossref pmid

4. Hidaka BH. 2012; Depression as a disease of modernity: explanations for increasing prevalence. J Affect Disord. 140:205–214.
crossref pmid pmc

5. Tiemeier H. 2003; Biological risk factors for late life depression. Eur J Epidemiol. 18:745–750.
crossref pmid

6. Torres GE, Gainetdinov RR, Caron MG. 2003; Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 4:13–25.
crossref pmid

7. Baldessarini RJ. 1975; The basis for amine hypotheses in affective disorder, A critical evaluation. Arch Gen Psychiatry. 32:9. 1087–1093.
crossref pmid

8. Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W. 1987; Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 238:4826. 522–524.
crossref pmid

9. Lee MS. 2000; Antidepressants and related drug interactions. Koeran J Biol Psychiatry. 7:1. 21–33.


10. Sarko J. 2000; Antidepressants, old and new. A review of their adverse effects and toxicity in overdose. Emerg Med Clin North Am. 18:637–654.
crossref pmid

11. Maes M. 1995; Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry. 19:1. 11–38.
crossref pmid

12. Song HR, Woo YS, Bahk WM. 2013; Depression as an inflammatory disease. Korean J Psychopharmacol. 24:1. 5–10.


13. Oh HM, Kim SW, Oh YT, Son CG, Lee JS. 2017; A comparative study on physiopathology of depression by Korean medicine and conventional medicine. Journal of Haehwa Medicine. 26:1. 11–18.


14. Kim ES. 2011; A study on the concept of Ul(鬱) in medical history-Focused on the theory submitted by Zhang-Zihe(張子和). J Oriental Medical Classics. 24:1. 73–84.


15. Mao QQ, Ip SP, Xian YF, Hu Z, Che CT. 2012; Anti-depressant-like effect of peony: a minireview. Pharmaceutical Biology. 50:72–77.
crossref pmid

16. Yoon JP. 2011. Evaluation of the remedy for neuronal diseases from Rhemannia glutinosa Liboschitz and elucidation of their underlying mechanisms. MS Thesis. Daegu Haany University;Daegu, Korea:


17. Kim JK, Cho BK. 1995. Oriental traditional medicine primaries book. Seoul: Younglim.


18. Liu ZY. 1984; Comparison of monosaccharide contents between the raw and prepared roots of Rehmannia. Zhong Yao Tong Bao. 9:17–18.
pmid

19. Ni M, Bian B, Wang H. 1992; Constituents of the dry roots of Rehmannia glutinosa Libosch. Zhongguo Zhong Yao Za Zhi. 17:297–298.
pmid

20. Min AY, Son AY, Kim HJ, Shin SK, Kim MR. 2015; Quality characteristics and antioxidant activities of noodles added with Rehmanniae Radix Preparata powder. J Korean Soc Food Sci Nutr. 44:3. 386–392.
crossref

21. Kong F, Lee BH, Wei K. 2019; 5-Hydroxymethylfurfural mitigates lipopolysaccharide-stimulated inflammation via suppression of MAPK, NF-κB and mTOR activation in RAW 264.7 cells. Molecules. 24:2. 275
crossref pmc

22. Custódio CS, Mello BSF, Cordeiro RC, de Araújo FYR, Chaves JH, Vasconcelos SMM, et al. Time course of the effects of lipopolysaccharide on prepulse inhibition and brain nitrite content in mice. Eur J Pharmacol. 2013; 713:31–38.
crossref pmid

23. Detke MJ, Rickels M, Lucki I. 1995; Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology. 121:1. 66–72.
crossref pmid

24. Hsiao YT, Yi PL, Li CL, Chang FC. 2012; Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology. 62:1. 373–384.
crossref pmid

25. Mao QQ, Ip SP, Ko KM, Tsai SH, Che CT. 2009; Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: Effects on hypothalamic- pituitary adrenal function and brain-derived neurotrophic factor. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 33:7. 1211–1216.
crossref pmid

26. Stetler C, Miller GE. 2011; Depression and hypothalamic-pituitary adrenal activation: a quantitative summary of four decades of research. Psychosom Med. 73:114–126.
crossref pmid

27. Schiepers OJ, Wichers MC, Maes M. 2005; Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 29:201–217.
crossref pmid

28. Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J. 2007; Neurobiology of depression: an integrated view of key findings. Int J Clin Pract. 61:2030–2040.
crossref pmid pmc

29. Dantzer R, O’Connor JC, Lawson MA, Kelley KW. 2011; Inflammation-associated depression: From serotonin to kynurenine. Psychoneuroendocrinology. 36:3. 426–436.
crossref pmid

30. Lee JE, Kwon YJ, Cho SH. 2011; A review of clinical studies with herbal medicine for depression - based on randomized controlled clinical trial. J of Oriental Neuropsychiatry. 22:4. 31–40.
crossref

31. Son SH, Son PI. 1985. Shinnongboncho-Gyeong. Taipei: Oju Publisher.


32. San S. 1994. Bonchdogyong. Hefei: Anhui Science and Technology Publisher.


33. Park SJ, Park HS, Yoo SO. 1998; Effects of supplemention of Rehmannia Radix on performance and physiological status in broiler chicks. Korean J Poult Sci. 25:195–202.


34. Tomoda M, Miyamoto H, Shimizu N. 1994; Structural features and anti-complementary activity of rehmannan SA, a polysaccharide from the root of Rehmannia glutinosa . Chem Pharm Bull. 42:1666–1668.
crossref

35. You BR, Kim HR, Kim HJ, Lee JY, Lee SY, Song MR, et al. 2011; Catalpol content and antioxidant activities in various cultivars of Rehmannia glutinosa . J Korean Soc Food Sci Nutr. 40:481–485.
crossref

36. Oh HL, You BR, Kim HJ, Lee JY, Kim NY, Song JE, et al. 2011; Quality characteristics and antioxidant activities of Rhmanniae Radix paste. J Korean Soc Food Sci Nutr. 40:1518–1524.
crossref

37. Cho SI. 2005; Effects of the Rehmanniae Radix Preparat on Ovariectomized Rats. Kor J Herbol. 20:4. 61–67.


38. Thao D, Roger M, Susan V, Carl W. 2008. Lippincott’s Illustrated Reviews: Immunology. Seoul: Shinilbooks.


39. Abbas AK, Lichtman AH, Pillai S. 2008. Cellular and Molecular Immunology, 6/E. Seoul: Epublic.


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