Immunity x Echinacea
These articles are not intended to provide treatment recommendations for the ongoing epidemic.
Panax Ginseng is the “ultimate” reference immunostimulant in the Orient, whereas Western cultures have focused on Echinacea (Echinacea purpurea or Echinacea Angustifolia).
This pearl of Western phytotherapy is a plant of the Asteraceae family with flowers that resemble the daisy and whose heart is remarkable prominent. Moreover, it looks like a sea urchin, which gave the name to the plant: the name Echinacea comes from "echinos", meaning sea urchin in ancient Greek.
The root of the plant is particularly appreciated in a medical context, although sometimes they use the whole plant in the production of alcoholic extracts (mother tinctures). A choice that may have consequences on the molecular profile of the extract and thus on its properties.
1. ECHINACEA’S MAIN MOLECULES OF INTEREST
- considered to be the key molecules of Echinacea
- lipophilic molecules with good bioavailability and many properties
- present in all parts of the plant but more abundant in the root
- present in alcoholic extracts
- large sugar assemblies
- often identified as having an impact on the intestinal microbiota and immunostimulatory
- mainly present in the roots
- not very soluble in ethanol, therefore mother tinctures and other extracts of the same type are rarely rich in polysaccharides
- present in the powdered plant or certain aqueous extracts
1.3. Phenolic compounds
- Echinacea contains numerous phenolic compounds as do other medicinal plants
- the most interesting are caffeic acid derivatives such as echinacoside or chicoric acid
- present in the roots and aerial parts of the plant
- could potentially be interesting under certain conditions, for example: potentially superior antiviral activity
2. BEYOND THE MOLECULES OF THE PLANT
Some recent data seem to support an original theory explaining that a good part of the immunostimulatory activity of Echinacea is not due to the plant itself but to the endophyte organisms which colonize it [1-5].
It seems too early to determine how crucial the role of these organisms is. However, the results raise the question of the effectiveness of the plant in the absence of these organisms. If this hypothesis were to be confirmed, it would give crucial importance to the "totum" but also to the methods of preparation: fresh/dry plant, drying methods, ...
3. ECHINACEA & IMMUNITY
The traditional allegation of strengthening natural defenses are no longer a subject of discussion since the European Medicines Agency recognizes the scientific credibility of this application . However, the mechanisms underlying this property are a real Gordian knot. Indeed, a complete review of the bibliography on the properties of Echinacea and its active substances inevitably leads to contradictions that can be explained by the nature of the extracts tested.
3.1. Echinacea & Macrophages
The available data on the immunomodulatory properties of Echinacea are numerous . Most of them refer to the influence on innate immunity, on macrophages in particular. Nevertheless, these data may appear contradictory, depending on the type of extract used. Extracts rich in polysaccharide fraction generally tend to stimulate the activation of macrophages [8-11], while extracts rich in alkylamides tend to limit the inflammatory response [12-19].
A limitation of inflammation can seem contrary to immune defenses: less recruitment on the site of infection. Nevertheless, it allows limiting the extent of the symptoms linked to this response and "maintain the defenses" over time. An example is nasal congestion.
When it comes to phenolic compounds, we observe variations according to their nature. However, we mainly find anti-inflammatory properties, especially with cynarine. They are not necessarily linked to macrophages but they reinforce the overall effect [20-22]. Note that the direct antiviral effect of Echinacea is probably linked to these molecules. Therefore, the "richness" in phenolic acids should not be overlooked.
Does this mean that using a totum could lead to "properties that cancel each other out"? Not necessarily. Polysaccharides can play a positive role at various levels and in particular, with the intestinal microbiota like many polysaccharides. While alkylamides, by their bioavailability, play on inflammatory sites.
Whole plant extracts are not necessarily less efficient. Their diversity in phenolic compounds could well have a positive impact on antibacterial/antiviral activity and/or on the intestinal microbiota in the long term. On the other hand, it is difficult to have an extract that is simultaneously rich in alkylamides, in phenolic compounds and in polysaccharides. To choose is to give up.
3.2. Echinacea & other immune actors
Some studies report a positive activity on the activation of other cell types, in particular via chicoric acid, which has been identified as an activator of dendritic cells  and T-lymphocytes .
The data relating to Echinacea properties focus mainly on inflammation or its consequences. In particular, the anti-inflammatory dimension of alkylamide-rich extracts and the immunostimulatory properties of polysaccharides-rich extracts [25-27]. Therefore, the activity of Echinacea seems to focus on the first line of defense: innate immunity. This happens by stimulating immunity with certain active ingredients or by limiting inflammatory mechanisms with others.
3.3. And at molecular level?
At the molecular level, we find this duality between polysaccharides, which stimulate the production of molecules activating immunity and alkylamides, which promote the control of inflammation. Alkylamides do that in particular by stimulating IL-10 and inhibiting pro-inflammatory molecules [28-29]. Observations at the molecular level seem to validate the effects identified at the cellular level.
Note that certain alkylamides have been identified as agonists of the CB2 receptors responsible for the stimulation of the endocannabinoid pathways particularly present in the immune cells [30-32]. This activity is anything but trivial because it could, next to its effect on the macrophage, intervene with certain categories of lymphocytes and especially stimulate Tregs.
Treg stimulation is often associated with a form of immune system tolerance. However, there is some evidence to suggest that when T cells are more tolerant, they also tend to be more effective because they focus on high-level antigens affinity . It may not be impossible that this aspect is linked to the relationships between the body and its microbiota.
Finally, the impact on PPARs is a track that might be worth further investigation . Note that the connections between CB2 and PPAR are highlighted for other plant extracts that are considered to be immunomodulatory (Ginseng, Beta-caryophyllene...). This double action is explained by the fact that endocannabinoids (molecules of the body) have this double activity too.
For the record, cannabidiol (CBD) from cannabis (Cannabis sativa) is an antagonist of CB2 receptors and can therefore reduce the effects of Echinacea.
4. TOMORROW'S TRACKS
4.1. What type of extract?
oot or whole plant? Totum or alcoholic extract? It is difficult to decide because each type of extract has advantages in terms of active molecules. Some preparations are likely to be more abundant in molecular type than others.
For the richness in alkylamides:
An alcoholic extract of the roots contains more alkylamides than an alcoholic extract of the whole plant. However, the diversity of alkylamides is greater with the whole plant.
For the richness in polysaccharides:
An enriched aqueous extract contains more polysaccharides because they are poorly soluble in alcohol. Polysaccharides are mainly present in the roots.
For phenolic compounds:
Phenolic compounds are present in the root as well as in the aerial parts but in different proportions depending on the molecules. The exclusive intake of the root brings less "phenolic variety".
It is essential to understand that these are generalities. We can have a root extract very poor in alkylamides and an extract of the whole plant that contains much more. In the end, the molecular specifications of the ingredient will decide.
4.2. For which product?
The data described above tend to highlight an advantage of Echinacea. On one hand, it stimulates the defenses by stimulating the immune system and on the other hand it limits the impact of an infection by acting anti-inflammatory and anti-infective.
Therefore, we have an ingredient that has its place in a product intended for the "treatment" of winter ailments. In other words, when the person presents the first symptoms of a cold or when he/she suffers from recurrent infections in midwinter period.
Echinacea is slightly less suitable as a preventive product for daily "immune" health since global support requires a more integrative approach.
4.3. What to associate it with?
Echinacea is intended for a formula that supports a person with a cold. It would preferably be associated with ingredients that control of inflammatory symptoms and indirect support the immune system by antibacterial and/or antiviral action.
In Aromatherapy, we use essential oils rich in 1,8-cineole to limit the symptoms, possibly accompanied by oils rich in carvacrol/thymol for their powerful anti-infectious properties.
In phytotherapy, we can turn to the great classics that are Cape Geranium (Pelargonium sidoides) or Elderberry (Sambucus nigra).
For a formula intended for prevention over a limited period:
In Aromatherapy, an essential oil rich in 1,8-cineole is always justified in delicate periods. However, we should limit the dose of essential oils rich in carvacrol/thymol to prevent the disturbance of intestinal microbiota.
Also, we should consider essential oil of Clove (Eugenia caryophyllus / Syzygium aromaticum) that is rich in eugenol. The stimulating properties of eugenol on humoral immunity, namely the production of antibodies, have been demonstrated in various studies [35-37].
We can consider providing antiviral and immunostimulatory activity too. Purists would probably think of the Tea tree (Melaleuca alternifolia), but we could easily prefer marjoram (Origanum majorana).
In herbal medicine, we can opt for Lake Baikal skullcap (Scutellaria baicalensis) with powerful antiviral properties when it is rich in baicalin [38-43]. This active compound is a regulator of inflammation [44-48] and has positive effects on the microbiota intestinal .
If we do not have a quality supply (extremely rare), we can replace it with an extract rich in ursolic/oleanolic acids [50-53], like certain extracts of trilobed sage (Salvia triloba) or marjoram (Origanum majorana).
Finally, a ginseng (Panax ginseng) rich in bioactive ginsenosides (Rg3, Rg5, Rk1) as well as ginsan (polysaccharides present in the total but not in the alcoholic extracts) provides an excellent formula. This type of ginseng presents a myriad of properties regarding the immune sphere (see the following article).
Behind its appearance as "grandmother's remedy", Echinacea is a medicinal plant in all its splendor, showing off its many properties as well as its great molecular complexity.
It is possible to express a favorable opinion to this plant in the context of "winter ailments". It can be considered single or combined with other active ingredients for the development of more specialized products.
Nevertheless, in the case of a preventive formula intended to ensure optimal "immune health" and not to counter the beginnings of a little "winter disorder", we prefer its oriental alter ego whose regulatory effect on the immunity seems more suitable (see next article).
 Haron MH, Tyler HL, Chandra S, Moraes RM, Jackson CR, Pugh ND, Pasco DS (2019) – “Plant microbiome-dependent immune enhancing action of Echinacea purpurea is enhanced by soil organic matter content.“ Sci Rep. 2019 Jan 15;9(1):136. doi: 10.1038/s41598-018-36907-x.
 Haron MH, Tyler HL, Pugh ND, Moraes RM, Maddox VL, Jackson CR, Pasco DS (2016) – “Activities and Prevalence of Proteobacteria Members Colonizing Echinacea purpurea Fully Account for Macrophage Activation Exhibited by Extracts of This Botanical.” Planta Med. 2016 Sep;82(14):1258-65. doi: 10.1055/s-0042-108590. Epub 2016 Jun 10.
 Kaur A, Oberhofer M, Juzumaite M, Raja HA, Gulledge TV, Kao D, Faeth SH, Laster SM, Oberlies NH, Cech NB (2016) – “Secondary Metabolites from Fungal Endophytes of Echinacea purpurea Suppress Cytokine Secretion by Macrophage-Type Cells.” Nat Prod Commun. 2016 Jan;11(8):1143-1146.
 Todd DA, Gulledge TV, Britton ER, Oberhofer M, Leyte-Lugo M, Moody AN, Shymanovich T, Grubbs LF, Juzumaite M, Graf TN, Oberlies NH, Faeth SH, Laster SM, Cech NB. (2015) – “Ethanolic Echinacea purpurea Extracts Contain a Mixture of Cytokine-Suppressive and Cytokine-Inducing Compounds, Including Some That Originate from Endophytic Bacteria.” PLoS One. 2015 May 1;10(5):e0124276. doi: 10.1371/journal.pone.0124276. eCollection 2015.
 Pugh ND, Jackson CR, Pasco DS (2013) – “Total bacterial load within Echinacea purpurea, determined using a new PCR-based quantification method, is correlated with LPS levels and in vitro macrophage activity.” Planta Med. 2013 Jan;79(1):9-14. doi: 10.1055/s-0032-1328023. Epub 2012 Dec 4.
 European Medicine Agency HMPC (2014) – “Assessment report on Echinacea purpurea (L.) Moench., herba recens” EMA/HMPC/557979/2013
 Hudson JB (2011) – “Applications of the phytomedicine Echinacea purpurea (Purple Coneflower) in infectious diseases.” J Biomed Biotechnol. 2012;2012:769896. doi: 10.1155/2012/769896. Epub 2011 Oct 26.
 Fu A, Wang Y, Wu Y, Chen H, Zheng S, Li Y, Xu X, Li W (2017) – « Echinacea purpurea Extract Polarizes M1 Macrophages in Murine Bone Marrow-Derived Macrophages Through the Activation of JNK.” J Cell Biochem. 2017 Sep;118(9):2664-2671. doi: 10.1002/jcb.25875. Epub 2017 May 15.
 Sullivan AM, Laba JG, Moore JA, Lee TD (2008) – “Echinacea-induced macrophage activation.” Immunopharmacol Immunotoxicol. 2008;30(3):553-74.
 Goel V, Chang C, Slama J, Barton R, Bauer R, Gahler R, Basu T (2002) – « Echinacea stimulates macrophage function in the lung and spleen of normal rats.” J Nutr Biochem. 2002 Aug;13(8):487.
 Roesler J, Emmendörffer A, Steinmüller C, Luettig B, Wagner H, Lohmann-Matthes ML (1991) – “Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system.” Int J Immunopharmacol. 1991;13(7):931-41.
 Cech NB, Kandhi V, Davis JM, Hamilton A, Eads D, Laster SM (2010) – “Echinacea and its alkylamides: effects on the influenza A-induced secretion of cytokines, chemokines, and PGE₂ from RAW 264.7 macrophage-like cells.” Int Immunopharmacol. 2010 Oct;10(10):1268-78. doi: 10.1016/j.intimp.2010.07.009. Epub 2010 Jul 30.
 La Lone CA, Rizshsky L, Hammer KD, Wu L, Solco AK, Yum M, Nikolau BJ, Wurtele ES, Murphy PA, Kim M, Birt DF (2009) – “Endogenous levels of Echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages.” J Agric Food Chem. 2009 Oct 14;57(19):8820-30. doi: 10.1021/jf901202y.
 Chicca A, Raduner S, Pellati F, Strompen T, Altmann KH, Schoop R, Gertsch J (2009) – “Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts.” Int Immunopharmacol. 2009 Jul;9(7-8):850-8. doi: 10.1016/j.intimp.2009.03.006. Epub 2009 Mar 19.
 Zhai Z, Haney D, Wu L, Solco A, Murphy PA, Wurtele ES, Kohut ML, Cunnick JE (2007) – “Alcohol extracts of Echinacea inhibit production of nitric oxide and tumor necrosis factor-alpha by macrophages in vitro.” Food Agric Immunol. 2007 Sep;18(3-4):221-236.
 Lalone CA, Huang N, Rizshsky L, Yum MY, Singh N, Hauck C, Nikolau BJ, Wurtele ES, Kohut ML, Murphy PA, Birt DF (2010) – “Enrichment of Echinacea angustifolia with Bauer alkylamide 11 and Bauer ketone 23 increased anti-inflammatory potential through interference with cox-2 enzyme activity.” J Agric Food Chem. 2010 Aug 11;58(15):8573-84. doi: 10.1021/jf1014268.
 Stevenson LM, Matthias A, Banbury L, Penman KG, Bone KM, Leach DL, Lehmann RP (2005) – “Modulation of macrophage immune responses by Echinacea.” Molecules. 2005 Oct 31;10(10):1279-85.
 LaLone CA, Hammer KD, Wu L, Bae J, Leyva N, Liu Y, Solco AK, Kraus GA, Murphy PA, Wurtele ES, Kim OK, Seo KI, Widrlechner MP, Birt DF (2007) – “Echinacea species and alkamides inhibit prostaglandin E(2) production in RAW264.7 mouse macrophage cells.” J Agric Food Chem. 2007 Sep 5;55(18):7314-22. Epub 2007 Aug 15.
 Matthias A, Banbury L, Stevenson LM, Bone KM, Leach DN, Lehmann RP (2007) – “Alkylamides from echinacea modulate induced immune responses in macrophages.” Immunol Invest. 2007;36(2):117-30.
 Hueza IM, Gotardo AT, da Silva Mattos MI, Górniak SL (2019) – “Immunomodulatory effect of Cynara scolymus (artichoke) in rats.” Phytother Res. 2019 Jan;33(1):167-173. doi: 10.1002/ptr.6210. Epub 2018 Oct 24.
 Fonseca FN, Papanicolaou G, Lin H, Lau CB, Kennelly EJ, Cassileth BR, Cunningham-Rundles S. (2014) – “Echinacea purpurea (L.) Moench modulates human T-cell cytokine response.” Int Immunopharmacol. 2014 Mar;19(1):94-102. doi: 10.1016/j.intimp.2013.12.019. Epub 2014 Jan 13.
 Dong GC, Chuang PH, Forrest MD, Lin YC, Chen HM (2006) – “Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method.” J Med Chem. 2006 Mar 23;49(6):1845-54.
 Li Y, Wang Y, Wu Y, Wang B, Chen X, Xu X, Chen H, Li W, Xu X (2017) – “Echinacea pupurea extracts promote murine dendritic cell maturation by activation of JNK, p38 MAPK and NF-κB pathways.” Dev Comp Immunol. 2017 Aug;73:21-26. doi: 10.1016/j.dci.2017.03.002. Epub 2017 Mar 2.
 Kour K, Bani S (2011) – “Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice.” Neuropharmacology. 2011 May;60(6):852-60. doi: 10.1016/j.neuropharm.2011.01.001. Epub 2011 Jan 25.
 Fonseca FN, Papanicolaou G, Lin H, Lau CB, Kennelly EJ5, Cassileth BR, Cunningham-Rundles S (2014) – “Echinacea purpurea (L.) Moench modulates human T-cell cytokine response.” Int Immunopharmacol. 2014 Mar;19(1):94-102. doi: 10.1016/j.intimp.2013.12.019. Epub 2014 Jan 13.
 Benson JM, Pokorny AJ, Rhule A, Wenner CA, Kandhi V, Cech NB, Shepherd DM (2010) – “Echinacea purpurea extracts modulate murine dendritic cell fate and function.” Food Chem Toxicol. 2010 May;48(5):1170-7. doi: 10.1016/j.fct.2010.02.007. Epub 2010 Feb 10.
 Ghaemi A, Soleimanjahi H, Gill P, Arefian E, Soudi S, Hassan Z (2009) – "Echinacea purpurea polysaccharide reduces the latency rate in herpes simplex virus type-1 infections.” Intervirology. 2009;52(1):29-34. doi: 10.1159/000212988. Epub 2009 Apr 17.
 Sasagawa M, Cech NB, Gray DE, Elmer GW, Wenner CA (2006) – “Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells.” Int Immunopharmacol. 2006 Jul;6(7):1214-21. Epub 2006 Mar 7.
 Yao L, Bai L, Tan Y, Sun J, Qu Q, Shi D, Guo S, Liu C (2019) – “The immunoregulatory effect of sulfated Echinacea purpurea polysaccharide on chicken bone marrow-derived dendritic cells.” Int J Biol Macromol. 2019 Oct 15;139:1123-1132. doi: 10.1016/j.ijbiomac.2019.08.028. Epub 2019 Aug 5.
 Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, Altmann KH, Gertsch J (2006) – “Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects.” J Biol Chem. 2006 May 19;281(20):14192-206. Epub 2006 Mar 17.
 Woelkart K, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R (2005) – “The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots.” Planta Med. 2005 Aug;71(8):701-5.
 Gertsch J, Schoop R, Kuenzle U, Suter A (2004) – “Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways.” FEBS Lett. 2004 Nov 19;577(3):563-9.
 Pace L, Tempez A, Arnold-Schrauf C, Lemaitre F, Bousso P, Fetler L, Sparwasser T, Amigorena S (2012) – « Regulatory T cells increase the avidity of primary CD8+ T cell responses and promote memory.” Science. 2012 Oct 26;338(6106):532-6. doi: 10.1126/science.1227049.
 Spelman K, Iiams-Hauser K, Cech NB, Taylor EW, Smirnoff N, Wenner CA (2009) – “Role for PPARgamma in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide.” Int Immunopharmacol. 2009 Oct;9(11):1260-4. doi: 10.1016/j.intimp.2009.08.009. Epub 2009 Aug 25.
 Dibazar SP, Fateh S, Daneshmandi S (2014) – “Clove (Syzygium aromaticum) ingredients affect lymphocyte subtypes expansion and cytokine profile responses: An in vitro evaluation.” J Food Drug Anal. 2014 Dec;22(4):448-454. doi: 10.1016/j.jfda.2014.04.005. Epub 2014 Oct 28.
 Halder S, Mehta AK, Mediratta PK, Sharma KK (2011) – “Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.” Phytother Res. 2011 Aug;25(8):1254-6. doi: 10.1002/ptr.3412. Epub 2011 Feb 1.
 Carrasco FR, Schmidt G, Romero AL, Sartoretto JL, Caparroz-Assef SM, Bersani-Amado CA, Cuman RK (2009) – “Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses.” J Pharm Pharmacol. 2009 Jul;61(7):961-7. doi: 10.1211/jpp/61.07.0017.
 Li R, Wang L (2019) – “Baicalin inhibits influenza virus A replication via activation of type I IFN signaling by reducing miR 146a.” Mol Med Rep. 2019 Dec;20(6):5041-5049. doi: 10.3892/mmr.2019.10743. Epub 2019 Oct 15.
 Oo A, Teoh BT, Sam SS, Bakar SA, Zandi K (2019) – “Baicalein and baicalin as Zika virus inhibitors.” Arch Virol. 2019 Feb;164(2):585-593. doi: 10.1007/s00705-018-4083-4. Epub 2018 Nov 3.
 Qian K, Kong ZR, Zhang J, Cheng XW, Wu ZY, Gu CX, Shao HX, Qin AJ. (2018) – “Baicalin is an inhibitor of subgroup J avian leukosis virus infection.” Virus Res. 2018 Mar 15;248:63-70. doi: 10.1016/j.virusres.2018.02.017. Epub 2018 Feb 23.
 Li X, Liu Y, Wu T, Jin Y, Cheng J, Wan C, Qian W, Xing F, Shi W (2015) – “The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro.” Viruses. 2015 Aug 19;7(8):4756-71. doi: 10.3390/v7082841.
 Ding Y, Dou J, Teng Z, Yu J, Wang T, Lu N, Wang H, Zhou C (2014) – “Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase.” Arch Virol. 2014 Dec;159(12):3269-78. doi: 10.1007/s00705-014-2192-2. Epub 2014 Jul 31.
 Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, Cheng VC, Tsui WH, Hung IF, Lee TS, Guan Y, Peiris JS, Yuen KY (2004) – “In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.” J Clin Virol. 2004 Sep;31(1):69-75.
 Meng X, Hu L, Li W (2019) – “Baicalin ameliorates lipopolysaccharide-induced acute lung injury in mice by suppressing oxidative stress and inflammation via the activation of the Nrf2-mediated HO-1 signaling pathway.” Naunyn Schmiedebergs Arch Pharmacol. 2019 Jul 4. doi: 10.1007/s00210-019-01680-9.
 Zhi HJ, Zhu HY, Zhang YY, Lu Y, Li H, Chen DF (2019) – “In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus.” Phytomedicine. 2019 Apr;57:105-116. doi: 10.1016/j.phymed.2018.12.009. Epub 2018 Dec 10.
 Peng LY, Yuan M, Song K, Yu JL, Li JH, Huang JN, Yi PF, Fu BD, Shen HQ (2019) – “Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κB pathway activation.” Int Immunopharmacol. 2019 Jul;72:467-472. doi: 10.1016/j.intimp.2019.04.046. Epub 2019 Apr 28.
 Deng J, Wang DX, Liang AL, Tang J, Xiang DK (2017) – “Effects of baicalin on alveolar fluid clearance and α-ENaC expression in rats with LPS-induced acute lung injury.” Can J Physiol Pharmacol. 2017 Feb;95(2):122-128. doi: 10.1139/cjpp-2016-0212. Epub 2016 Aug 31.
 Shi H, Ren K, Lv B, Zhang W, Zhao Y, Tan RX, Li E (2016) – “Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice.” Sci Rep. 2016 Oct 21;6:35851. doi: 10.1038/srep35851.
 Shin NR, Gu N, Choi HS, Kim H (2020) – “Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation.” Am J Physiol Endocrinol Metab. 2020 Jan 1;318(1):E52-E61. doi: 10.1152/ajpendo.00221.2019. Epub 2019 Nov 26.
 Tohmé MJ, Giménez MC, Peralta A, Colombo MI, Delgui LR (2019) – “Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro.” Int J Antimicrob Agents. 2019 Nov;54(5):601-609. doi: 10.1016/j.ijantimicag.2019.07.015. Epub 2019 Jul 26.
 Woźniak Ł, Skąpska S, Marszałek K (2015) – “Ursolic Acid--A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities.” Molecules. 2015 Nov 19;20(11):20614-41. doi: 10.3390/molecules201119721.
 Kong L, Li S, Liao Q, Zhang Y, Sun R, Zhu X, Zhang Q, Wang J, Wu X, Fang X, Zhu Y (2013) – “Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity.” Antiviral Res. 2013 Apr;98(1):44-53. doi: 10.1016/j.antiviral.2013.02.003. Epub 2013 Feb 16.
 Wan SZ, Liu C, Huang CK, Luo FY, Zhu X (2019) – “Ursolic Acid Improves Intestinal Damage and Bacterial Dysbiosis in Liver Fibrosis Mice.” Front Pharmacol. 2019 Nov 1;10:1321. doi: 10.3389/fphar.2019.01321. eCollection 2019.