Journal of Korean Medicine for Obesity Research (한방비만학회지)

The Society of Korean Medicine for obesity Research (한방비만학회)
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The Effect of Long Coronavirus Disease on Obesity and the Role of Korean Medicine

롱코비드가 비만에 미치는 영향과 그에 대한 한의학의 역할

  • Han, Kyungsun (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Kim, Myung-Ho (Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School)
  • 한경선 (한국한의학연구원 한의과학연구부) ;
  • 김명호 (하버드의과대학 부속 매사추세츠종합병원 소화기내과 간센터)
  • Received : 2022.05.19
  • Accepted : 2022.06.13
  • Published : 2022.06.30
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Abstract

While the Coronavirus disease 2019 (COVID-19) pandemic is gradually turning into an endemic disease, concerns about post COVID-19 conditions (Long COVID) are emerging. Obesity is a major risk factor for severe complications of COVID-19, and COVID-19 has a wide range of effects on obesity and metabolic function. This paper aims to examine the interaction between COVID-19 and obesity, the effects and mechanisms of long COVID on obesity, and the role of Korean medicine on long COVID-related obesity. Obesity may worsen with cardiometabolic damage and psychosocial insecurity during COVID-19 and long COVID-induced neuroinflammation, systemic inflammation, mitochondrial dysfunction, and hypoxia also may aggravate obesity. Korean Medicine treatments, which have been widely used to treat obesity, have the potential to improve obesity in the era of long COVID by intervening in these mechanisms.

Keywords

Acknowledgement

이 논문은 2022년도 한국한의학연구원의 주요사업인 한의의료기술의 임상근거 강화(KSN2022210)의 지원을 받아 수행된 연구임.

References

  1. Stefan N, Birkenfeld AL, Schulze MB. Global pandemics interconnected-obesity, impaired metabolic health and COVID-19. Nature Reviews Endocrinology. 2021 ; 17(3) : 135-49. https://doi.org/10.1038/s41574-020-00462-1
  2. Banerjee M, Gupta S, Sharma P, Shekhawat J, Gauba K. Obesity and COVID-19: a fatal alliance. Indian Journal of Clinical Biochemistry. 2020 ; 35(4) : 410-7. https://doi.org/10.1007/s12291-020-00909-2
  3. Aghili SMM, Ebrahimpur M, Arjmand B, Shadman Z, Pejman Sani M, Qorbani M, et al. Obesity in COVID-19 era, implications for mechanisms, comorbidities, and prognosis: a review and meta-analysis. International Journal of Obesity. 2021 ; 45(5) : 998-1016. https://doi.org/10.1038/s41366-021-00776-8
  4. Cava E, Neri B, Carbonelli MG, Riso S, Carbone S. Obesity pandemic during COVID-19 outbreak: Narrative review and future considerations. Clinical Nutrition. 2021 ; 40(4) : 1637-43. https://doi.org/10.1016/j.clnu.2021.02.038
  5. Lim S, Shin SM, Nam GE, Jung CH, Koo BK. Proper management of people with obesity during the COVID-19 pandemic. Journal of Obesity & Metabolic Syndrome. 2020 ; 29(2) : 84. https://doi.org/10.7570/jomes20056
  6. Clemmensen C, Petersen MB, Sorensen TIA. Will the COVID-19 pandemic worsen the obesity epidemic? Nat Rev Endocrinol. 2020 ; 16(9) : 469-70. https://doi.org/10.1038/s41574-020-0387-z
  7. Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. Bmj. 2021 ; 374 : n1648.
  8. Korea Institute of Oriental Medicine, Obesity Korean medicine clinical practice guideline. Seoul : Elsevier Korea. 2016.
  9. Stefan N, Birkenfeld AL, Schulze MB, Ludwig DS. Obesity and impaired metabolic health in patients with COVID-19. Nat Rev Endocrinol. 2020 ; 16(7) : 341-2. https://doi.org/10.1038/s41574-020-0364-6
  10. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020 ; 12(4) : 988. https://doi.org/10.3390/nu12040988
  11. Teymoori-Rad M, Shokri F, Salimi V, Marashi SM. The interplay between vitamin D and viral infections. Rev Med Virol. 2019 ; 29(2) : 2032.
  12. Watanabe M, Risi R, Tuccinardi D, Baquero CJ, Manfrini S, Gnessi L. Obesity and SARS-CoV-2: a population to safeguard. Diabetes Metab Res Rev. 2020 ; 36(7) : 3325.
  13. Muscogiuri G, Pugliese G, Barrea L, Savastano S, Colao A. Commentary: obesity: the "Achilles heel" for COVID-19? Metabolism. 2020 ; 108 : 154251. https://doi.org/10.1016/j.metabol.2020.154251
  14. Karkhaneh M, Qorbani M, Mohajeri-Tehrani MR, Hoseini S. Association of serum complement C3 with metabolic syndrome components in normal weight obese women. J Diabetes Metab Disord. 2017 ; 16 : 49. https://doi.org/10.1186/s40200-017-0330-6
  15. Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS One. 2015 ; 10(7) : 0133494.
  16. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 ; 46(5) : 846-8. https://doi.org/10.1007/s00134-020-05991-x
  17. Jose RJ, Manuel A. Does coronavirus disease 2019 disprove the obesity paradox in acute respiratory distress syndrome? Obesity (Silver Spring). 2020 ; 28(6) : 1007. https://doi.org/10.1002/oby.22835
  18. Michalakis K, Ilias I. SARS-CoV-2 infection and obesity: common inflammatory and metabolic aspects. Diabetes Metab Syndr. 2020 ; 14(4) : 469-71. https://doi.org/10.1016/j.dsx.2020.04.033
  19. Zhang AJ, To KK, Li C, Lau CC, Poon VK, Chan CC, et al. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A (H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J Infect Dis. 2013 ; 207(8) : 1270-80. https://doi.org/10.1093/infdis/jit031
  20. Maier HE, Lopez R, Sanchez N, Ng S, Gresh L, Ojeda S, et al. Obesity increases the duration of influenza A virus shedding in adults. J Infect Dis. 2018 ; 218(9) : 1378-82. https://doi.org/10.1093/infdis/jiy370
  21. A hn SY, Sohn SH, Lee SY, Park HL, Park YW, Kim H, et al. The effect of lipopolysaccharide-induced obesity and its chronic inflammation on influenza virus-related pathology. Environ Toxicol Pharmacol. 2015 ; 40(3) : 924-30. https://doi.org/10.1016/j.etap.2015.09.020
  22. Pasarica M, Dhurandhar NV. Infectobesity: obesity of infectious origin. Advances in Food and Nutrition Research. 2007 ; 52 : 61-102. https://doi.org/10.1016/S1043-4526(06)52002-9
  23. Bailin SS, Gabriel CL, Wanjalla CN, Koethe JR. Obesity and weight gain in persons with HIV. Current HIV/AIDS Reports. 2020 ; 17(2) : 138-50. https://doi.org/10.1007/s11904-020-00483-5
  24. Atkinson R, Dhurandhar N, Allison D, Bowen R, Israel B, Albu J, et al. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. International Journal of Obesity. 2005 ; 29(3) : 281-6. https://doi.org/10.1038/sj.ijo.0802830
  25. Bassols J, Moreno JM, Ortega F, Ricart W, Fernandez-Real JM. Characterization of herpes virus entry mediator as a factor linked to obesity. Obesity. 2010 ; 18(2) : 239-46. https://doi.org/10.1038/oby.2009.250
  26. Bianchi F, Duque ALRF, Saad SMI, Sivieri K. Gut microbiome approaches to treat obesity in humans. Applied Microbiology and Biotechnology. 2019 ; 103(3) : 1081-94. https://doi.org/10.1007/s00253-018-9570-8
  27. Dhurandhar NV. Contribution of pathogens in human obesity. Drug News & Perspectives. 2004 ; 17(5) : 307-13. https://doi.org/10.1358/dnp.2004.17.5.829034
  28. Dhurandhar N, Bailey D, Thomas D. Interaction of obesity and infections. Obesity Reviews. 2015 ; 16(12) : 1017-29. https://doi.org/10.1111/obr.12320
  29. Tian Y, Jennings J, Gong Y, Sang Y. Viral infections and interferons in the development of obesity. Biomolecules. 2019 ; 9(11) : 726. https://doi.org/10.3390/biom9110726
  30. Sun L, Ma L, Ma Y, Zhang F, Zhao C, Nie Y. Insights into the role of gut microbiota in obesity: pathogenesis, mechanisms, and therapeutic perspectives. Protein Cell. 2018 ; 9(5) : 397-403. https://doi.org/10.1007/s13238-018-0546-3
  31. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 ; 395(10234) : 1417-8. https://doi.org/10.1016/s0140-6736(20)30937-5
  32. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020 ; 383(2) : 120-8. https://doi.org/10.1056/NEJMoa2015432
  33. Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and proposed management of the acute COVID19 cardiovascular syndrome. Circulation. 2020 ; 141(23) : 1903-14. https://doi.org/10.1161/CIRCULATIONAHA.120.047349
  34. Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, Lim JK. Abnormal liver tests in COVID-19: a retrospective observational cohort study of 1,827 patients in a major U.S. hospital network. Hepatology. 2020 ; 72(4) : 1169-76. https://doi.org/10.1002/hep.31487
  35. Bertolini A, van de Peppel IP, Bodewes F, Moshage H, Fantin A, Farinati F, et al. Abnormal liver function tests in patients with COVID-19: relevance and potential pathogenesis. Hepatology. 2020 ; 72(5) : 1864-72. https://doi.org/10.1002/hep.31480
  36. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 ; 47(3) : 193-9. https://doi.org/10.1007/s00592-009-0109-4
  37. Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z. ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection. Clin Gastroenterol Hepatol. 2020 ; 18(9) : 2128-30. https://doi.org/10.1016/j.cgh.2020.04.040
  38. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 ; 97(5) : 829-38. https://doi.org/10.1016/j.kint.2020.03.005
  39. Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel Coronavirus 2019 epidemic and kidneys. Kidney Int. 2020 ; 97(5) : 824-8. https://doi.org/10.1016/j.kint.2020.03.001
  40. Puelles VG, Lutgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med. 2020 ; 383(6) : 590-2. https://doi.org/10.1056/NEJMc2011400
  41. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020 ; 26(7) : 1017-32. https://doi.org/10.1038/s41591-020-0968-3
  42. Wang C, Yu C, Jing H, Wu X, Novakovic VA, Xie R, et al. Long COVID: the nature of thrombotic sequelae determines the necessity of early anticoagulation. Frontiers in Cellular and Infection Microbiology. 2022 ; 12: 861703. https://doi.org/10.3389/fcimb.2022.861703
  43. Kim D, Subramanian SV, Gortmaker SL, Kawachi I. US state- and county-level social capital in relation to obesity and physical inactivity: a multilevel, multivariable analysis. Soc Sci Med. 2006 ; 63(4) : 1045-59. https://doi.org/10.1016/j.socscimed.2006.02.017
  44. Higgs S, Thomas J. Social influences on eating. Current Opinion in Behavioral Sciences. 2016 ; 9 : 1-6. https://doi.org/10.1016/j.cobeha.2015.10.005
  45. Yanovski JA, Yanovski SZ, Sovik KN, Nguyen TT, O'Neil PM, Sebring NG. A prospective study of holiday weight gain. N Engl J Med. 2000 ; 342(12) : 861-7. https://doi.org/10.1056/NEJM200003233421206
  46. Peterman JN, Wilde PE, Liang S, Bermudez OI, Silka L, Rogers BL. Relationship between past food deprivation and current dietary practices and weight status among Cambodian refugee women in Lowell, MA. Am J Public Health. 2010 ; 100(10) : 1930-7. https://doi.org/10.2105/AJPH.2009.175869
  47. National Institute for Health and Care Excellence. COVID19 rapid guideline: managing the long-term effects of COVID-19 NICE guideline [Internet]. 2020 [cited 2022 May 1]. Available from: https://www.nice.org.uk/guidance/ng188.
  48. Datta SD, Talwar A, Lee JT. A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: illness beyond acute infection and public health implications. JAMA. 2020 ; 324(22) : 2251-2. https://doi.org/10.1001/jama.2020.22717
  49. Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, et al. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021 ; 114(9) : 428-42. https://doi.org/10.1177/01410768211032850
  50. Vimercati L, De Maria L, Quarato M, Caputi A, Gesualdo L, Migliore G, et al. Association between long COVID and overweight/obesity. J Clin Med. 2021 ; 10(18) : 10184143.
  51. Aminian A, Bena J, Pantalone KM, Burguera B. Association of obesity with postacute sequelae of COVID-19. Diabetes Obes Metab. 2021 ; 23(9) : 2183-8. https://doi.org/10.1111/dom.14454
  52. Umesh A, Pranay K, Pandey RC, Gupta MK. Evidence mapping and review of long- COVID and its underlying pathophysiological mechanism. Infection. 2022 ; 50 : 1-14. https://doi.org/10.1007/s15010-021-01659-w
  53. Talen MR, Mann MM. Obesity and mental health. Primary Care: Clinics in Office Practice. 2009 ; 36(2) : 287-305. https://doi.org/10.1016/j.pop.2009.01.012
  54. Sarwer DB, Polonsky HM. The psychosocial burden of obesity. Endocrinol Metab Clin North Am. 2016 ; 45(3) : 677-88. https://doi.org/10.1016/j.ecl.2016.04.016
  55. Bailey EK, Steward KA, VandenBussche Jantz AB, Kamper JE, Mahoney EJ, Duchnick JJ. Neuropsychology of COVID-19: anticipated cognitive and mental health outcomes. Neuropsychology. 2021 ; 35(4) : 335-51. https://doi.org/10.1037/neu0000731
  56. Woo MS, Malsy J, Pottgen J, Seddiq Zai S, Ufer F, Hadjilaou A, et al. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Communications. 2020 ; 2(2) : 1-9.
  57. Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nature Neuroscience. 2021 ; 24(2) : 168-75. https://doi.org/10.1038/s41593-020-00758-5
  58. Daniels BP, Holman DW, Cruz-Orengo L, Jujjavarapu H, Durrant DM, Klein RS. Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals. MBio. 2014 ; 5(5) : 1-13. https://doi.org/10.3391/mbi.2014.5.1.01
  59. Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neuroscience & Therapeutics. 2021 ; 27(1) : 36-47. https://doi.org/10.1111/cns.13569
  60. Kim MH, Salloum S, Wang JY, Wong LP, Regan J, Lefteri K, et al. Type I, II, and III interferon signatures correspond to Coronavirus disease 2019 severity. J Infect Dis. 2021 ; 224(5) : 777-82. https://doi.org/10.1093/infdis/jiab288
  61. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. 2021 ; 78(6) : 682-3. https://doi.org/10.1001/jamapsychiatry.2021.0500
  62. Karczewski J, Sledzinska E, Baturo A, Jonczyk I, Maleszko A, Samborski P, et al. Obesity and inflammation. European Cytokine Network. 2018 ; 29(3) : 83-94. https://doi.org/10.1684/ecn.2018.0415
  63. Ma M-J, Qiu S-F, Cui X-M, Ni M, Liu H-J, Ye R-Z, et al. Persistent SARS-CoV-2 infection in asymptomatic young adults. Signal Transduction and Targeted Therapy. 2022 ; 7(1) : 77. https://doi.org/10.1038/s41392-022-00931-1
  64. Moran E, Cook T, Goodman AL, Gupta RK, Jolles S, Menon DK, et al. Persistent SARS-CoV-2 infection: the urgent need for access to treatment and trials. Lancet Infect Dis. 2021 ; 21(10) : 1345-7. https://doi.org/10.1016/S1473-3099(21)00464-3
  65. Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nature Immunology. 2022 ; 23(2) : 210-6. https://doi.org/10.1038/s41590-021-01113-x
  66. de Mello AH, Costa AB, Engel JDG, Rezin GT. Mitochondrial dysfunction in obesity. Life Sciences. 2018 ; 192 : 26-32. https://doi.org/10.1016/j.lfs.2017.11.019
  67. Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: a possible approach to SARS-CoV-2 'long-haulers'? Chronic Dis Transl Med. 2021 ; 7(1) : 14-26.
  68. Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2021 ; 118(34) : 2024358118.
  69. de Boer E, Petrache I, Goldstein NM, Olin JT, Keith RC, Modena B, et al. Decreased fatty acid oxidation and altered lactate production during exercise in patients with post-acute COVID-19 syndrome. Am J Respir Crit Care Med. 2022 ; 205(1) : 126-9. https://doi.org/10.1164/rccm.202108-1903LE
  70. Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007 ; 293(4) : 1118-28. https://doi.org/10.1152/ajpendo.00435.2007
  71. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes. 2009 ; 58(3) : 718-25. https://doi.org/10.2337/db08-1098
  72. Lee YS, Kim JW, Osborne O, Oh DY, Sasik R, Schenk S, et al. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell. 2014 ; 157(6) : 1339-52. https://doi.org/10.1016/j.cell.2014.05.012
  73. Mazzatti D, Lim FL, O'Hara A, Wood IS, Trayhurn P. A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes. Arch Physiol Biochem. 2012 ; 118(3) : 112-20. https://doi.org/10.3109/13813455.2012.654611
  74. Gaspar JM, Velloso LA. Hypoxia inducible factor as a central regulator of metabolism - implications for the development of obesity. Frontiers in Neuroscience. 2018 ; 12 : 813. https://doi.org/10.3389/fnins.2018.00813
  75. Lee K, Jeong S, Jeong M, Choi Y, Song M, Jang I. Review on herbal medicine treatment for late complications of COVID-19 patients. J Int Korean Med. 2021 ; 42(1) : 53-66. https://doi.org/10.22246/jikm.2021.42.1.53
  76. Liu J, Dong F, Robinson N. State-of-the-art evidence of traditional Chinese medicine for treating coronavirus disease 2019. Journal of Traditional Chinese Medical Sciences. 2022 ; 9(1) : 2-6. https://doi.org/10.1016/j.jtcms.2022.01.005
  77. Badakhsh M, Dastras M, Sarchahi Z, Doostkami M, Mir A, Bouya S. Complementary and alternative medicine therapies and COVID-19: a systematic review. Rev Environ Health. 2021 ; 36(3) : 443-50. https://doi.org/10.1515/reveh-2021-0012
  78. Park B-K, Kim NS, Kim YR, Yang C, Jung IC, Jang I-S, et al. Antidepressant and anti-neuroinflammatory effects of Bangpungtongsung-San. Frontiers in Pharmacology. 2020 ; 11 : 958. https://doi.org/10.3389/fphar.2020.00958
  79. Kim H-J, Park O-S, Kim K-S, Cha J-H, Kim Y-B. The effect of Bangpungtongsung-san on model of allergic rhinitis. The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology. 2006 ; 19(1) : 21-30.
  80. Lee CW, Kim SC, Kwak TW, Lee JR, Jo MJ, Ahn Y-T, et al. Anti-inflammatory effects of Bangpungtongsung-San, a traditional herbal prescription. Evidence-Based Complementary and Alternative Medicine. 2012 ; 2012 : 892943. https://doi.org/10.1155/2012/892943
  81. Lee M-Y, Shin I-S, Jeon W-Y, Shin N, Shin H-K. Bangpungtongseong-san, a traditional herbal medicine, attenuates chronic asthmatic effects induced by repeated ovalbumin challenge. International Journal of Molecular Medicine. 2014 ; 33(4) : 978-86. https://doi.org/10.3892/ijmm.2014.1654
  82. Park J-K, Shim J-Y, Cho A-R, Cho M-R, Lee Y-J. Korean red ginseng protects against mitochondrial damage and intracellular inflammation in an animal model of type 2 diabetes mellitus. Journal of Medicinal Food. 2018 ; 21(6) : 544-50. https://doi.org/10.1089/jmf.2017.4059
  83. Dong G-Z, Jang EJ, Kang SH, Cho IJ, Park S-D, Kim SC, et al. Red ginseng abrogates oxidative stress via mitochondria protection mediated by LKB1-AMPK pathway. BMC Complementary and Alternative Medicine. 2013 ; 13(1) : 1-9. https://doi.org/10.1186/1472-6882-13-1
  84. Shin SJ, Jeon SG, Kim J-I, Jeong Y-O, Kim S, Park YH, et al. Red ginseng attenuates Aβ-induced mitochondrial dysfunction and Aβ-mediated pathology in an animal model of Alzheimer's disease. International Journal of Molecular Sciences. 2019 ; 20(12) : 3030. https://doi.org/10.3390/ijms20123030
  85. Wang T, Li HT, Wei SZ, Cai HD, Zhu Y, Liu HH, et al. Use of network pharmacology and molecular docking to investigate the mechanism by which ginseng ameliorates hypoxia. Biomed Environ Sci. 2018 ; 31(11) : 855-8. https://doi.org/10.3967/bes2018.114
  86. Choi Y-J, Choi H, Cho C-H, Park J-W. Red ginseng deregulates hypoxia-induced genes by dissociating the HIF-1 dimer. Journal of Natural Medicines. 2011 ; 65(2) : 344-52. https://doi.org/10.1007/s11418-010-0504-8
  87. Lim W, Shim MK, Kim S, Lee Y. Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation. Phytomedicine. 2015 ; 22(6) : 597-604. https://doi.org/10.1016/j.phymed.2015.03.005
  88. Liu P, Zhao H, Luo Y. Anti-aging implications of Astragalus Membranaceus (Huangqi): a well-known Chinese tonic. Aging Dis. 2017 ; 8(6) : 868-86. https://doi.org/10.14336/AD.2017.0816
  89. Huang Y-F, Lu L, Zhu D-J, Wang M, Yin Y, Chen D-X, et al. Effects of astragalus polysaccharides on dysfunction of mitochondrial dynamics induced by oxidative stress. Oxidative Medicine and Cellular Longevity. 2016 ; 2016 : 9573291.
  90. Ma Q, Xu Y, Tang L, Yang X, Chen Z, Wei Y, et al. Astragalus polysaccharide attenuates cisplatin-induced acute kidney injury by suppressing oxidative damage and mitochondrial dysfunction. BioMed Research International. 2020 ; 2020 : 2851349.
  91. Cheng D, Yang X-J, Zhang L, Qin Z-S, Li W-Q, Xu H-C, et al. Tortoise plastron and deer antler gelatin prevents against neuronal mitochondrial dysfunction in vitro: implication for a potential therapy of Alzheimer's disease. Frontiers in Pharmacology. 2021 ; 12 : 1171.
  92. Ni Y, Wang Z, Ma L, Yang L, Wu T, Fu Z. Pilose antler polypeptides ameliorate inflammation and oxidative stress and improves gut microbiota in hypoxic-ischemic injured rats. Nutrition Research. 2019 ; 64 : 93-108. https://doi.org/10.1016/j.nutres.2019.01.005
  93. Ruan H, Wang L, Wang J, Sun H, He X, Li W, et al. Sika deer antler protein against acetaminophen-induced oxidative stress and apoptosis in HK-2 cells via activating Nrf2/keap1/HO-1 pathway. Journal of Food Biochemistry. 2019 ; 43(12) : 13067.
  94. Zhu W, Wang H, Zhang W, Xu N, Xu J, Li Y, et al. Protective effects and plausible mechanisms of antler-velvet polypeptide against hydrogen peroxide induced injury in human umbilical vein endothelial cells. Canadian Journal of Physiology and Pharmacology. 2017 ; 95(5) : 610-9. https://doi.org/10.1139/cjpp-2016-0196
  95. Yen T-L, Ong E-T, Lin K-H, Chang C-C, Jayakumar T, Lin S-C, et al. Potential advantages of Chinese medicine Taohong Siwu Decoction (桃红四物汤) combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats. Chinese Journal of Integrative Medicine. 2014 ; 20 : 1-9.
  96. Jinxia L, Xiaoqing Z, Caixing Z, Lina L, Ling L. Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis. Digital Chinese Medicine. 2021 ; 4(2) : 144-58. https://doi.org/10.1016/j.dcmed.2021.06.007
  97. Liu S, Wang Z, Su Y, Qi L, Yang W, Fu M, et al. A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis. Nature. 2021 ; 598(7882) : 641-5. https://doi.org/10.1038/s41586-021-04001-4
  98. Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, et al. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: a randomized controlled trial. EClinicalMedicine. 2022 ; 45 : 101300. https://doi.org/10.1016/j.eclinm.2022.101300
  99. Meng J-B, Jiao Y-N, Xu X-J, Lai Z-Z, Zhang G, JI C-L, et al. Electro-acupuncture attenuates inflammatory responses and intraabdominal pressure in septic patients: a randomized controlled trial. Medicine. 2018 ; 97(17) : 555.