Study	Methods	Population	Intervention	Outcomes
Perić et al. (2020) [66]	Prospective case–control study	26 patients with acute post-viral rhinosinusitis	3×/day 20 mg oral EPs 7630 tablets for 10 days	Chemokine levels in nasal secretions, nasal symptoms and endoscopic findings
Perić et al. (2021) [65]	Randomized prospective study	78 patients with uncomplicated acute bacterial rhinosinusitis	During 10 days: 26 patients received 3 × 20 mg/day EPs 7630 tablets; 26 patients received 2 × 150 mg/day roxithromysin tablets	Chemokine levels in nasal secretion and clinical parameters were compared on day 0 and day 10
Goel et al. (2005) [81]	Randomized, double-blind, placebo controlled trial	150 volunteers, aged 18–65 years, with a history of two or more infections of the common cold in the previous year	At the onset of a cold, on day 1 eight doses of 5 mL EchinilinTM (‘Factors R&D Technologies’, Burnaby, BC, Canada) were taken, and on the 6 consecutive days three doses/day	Self-assessed severity of cold symptoms during the 7 days
Dapas et al. (2014) [82]	Pilot study	10 healthy volunteers	10 mL Polinacea® (Indena, Milano, Italy) syrup/day during 1 month	Expression levels of IL-2, IL-8, IL-6, and TNF-α in lympho-monocytes and plasma samples
Ritchie et al. (2011) [83]	Intervention study	30 healthy volunteers	Five days of 4 × 1 mL, followed by 3 days of 10 × 1 mL Echinaforce®	Elastase, IL-1β, IL-6, IL-8, IL-10, IL-12 MCP-1, TNF-α, and IFN-γ in daily taken blood samples
Kim et al. (2002) [84]	Preliminary, randomized, double-blind, placebo-controlled trial	48 healthy female volunteers, aged 22–51 years	Daily, a combination of E. purpurea and E. angustifolia (E. purpurea whole herb extract 4% (908 mg/day), E. purpurea whole herb (464 mg/day) or E. angustifolia root (36 mg/day) during 4 weeks	Complement properdin, white blood cell count, neutrophils, lymphocytes, monocytes, quality of life assessment
Sheeja et al. (2006) [46]	Animal study	12 BALB/c mice	5 doses of 10 mg methanolic extract of A. paniculata for 5 days	PMA-induced superoxide and nitric oxide formation
Wang et al. (2010) [42]	Animal study	12 BALB/c mice	Intraperitoneal administration of 1 mg/kg/day andrographolide, during 7 days	Antibodies and IL-4-producing splenocytes
Mishra et al. (2013) [34]	In vitro	E. coli, P. aeruginosa, M. tuberculosis, S. Aureus, MRSA, and methicillin-resistant E. faecalis	Agar well diffusion with A. paniculata	MIC
Abubacker and Vasantha (2010) [36]	In vitro	E. coli, K. pneumoniae, P. vulgaris, and S. pneumoniae	Disc diffusion assay with A. paniculata	Inhibition zone
Rajalakshmi and Cathrine (2016) [33]	In vitro	E. coli, S. aureus, B. subtilis	Screening for phytochemical components of A. paniculata and disc diffusion assay	Inhibition zone
Xu et al. (2012) [37]	In vitro	S. epidermidis, P. aeruginosa, B. subtilis	Microtitre plate broth dilution with noriridoids from the roots of A. paniculata	MIC
Chandrasekaran et al. (2010) [44]	In vitro	J774A.1 murine macrophages	Effect of an extract of A. paniculata leaves on inflammatory response to LPS	Inhibition of NO, PGE2, IL-1β, and IL-6
Chandrasekaran et al. (2011) [43]	In vitro	J774A.1 macrophages	Effect of 7 phytoconstituents (andrographolide, neoandrographolide, isoandrographolide, andrograpanin, 14-deoxy-11,12-didehydroandrographolide, 7-O-methylwogonin, and skullcapflavone-I) isolated from A. paniculata on inflammatory mediators	NO, PGE2, IL-1β, IL-6, LTB4, TXB2, and histamine
Parichatikanond et al. (2010) [45]	In vitro	Ionophore A23 187-induced human platelets	The effect of diterpenoids from A. paniculata on the production of inflammatory cytokines and COX activities	COX-2 activity, TNF-α, IL-6, IL-1β, and IL-10, gene expression of cytokines and cytokine receptors
Liu et al. (2007) [41]	In vitro	L-929 cells and bone-marrow-derived macrophages from BALB-c mice	The effect of andrograpanin from A. paniculata on overproduction of NO, pro-inflammatory cytokines, and involved pathways	NO, TNF-, IL-6, and IL-12p70
Kumar et al. (2004) [40]	In vitro	Peripheral blood lymphocytes of healthy volunteers	Different fractions of methanolic extract of A. paniculata were screened for immunostimulatory effects	IL-2
Chen et al. (2009) [38]	Animal and in vitro study	BALB/c mice	Mice were infected with avian influenza A/chicken/Guang-dong/96 (H9N2) virus and A/duck/Guangdong/99 (H5N1) virus and different doses of A. paniculata were administered	LD50 of influenza virus in mice, lung virus titer, in vivo and in vitro antiviral evaluation, toxicity of A. paniculata
Conrad et al. (2007) [49]	In vitro	Human peripheral blood	The effect of EPs 7630 on the activity of human peripheral blood cells	Phagocytosis and oxidative burst
Janecki et al. (2011) [49]	In vitro	Human HEp-2 epithelial cells and group A-streptococci (GAS)	The effect of EPs 7630, the methanol and non-methanol fraction, on GAS adhesion to Hep-2 cells	Percentage of change in adhesion
Neugebauer et al. (2005) [57]	In vitro	Ciliated cell cultures of human epithelium	The effect of EPs 7630 on ciliary beat frequency	Percentage of change in ciliary beat frequency
Koch and Wohn (2007) [62]	In vitro	Human neutrophils and granulocytes	The effects of EPs 7630 in concentrations between 0.3 and 30 µg/mL after 5 h incubation on antibacterial peptide production	Antibacterial protein’s neutrophil peptides 1–3 and bactericidal/permeablity-increasing protein
Kayser et al. (2001) [59]	In vitro	Leishmania donovani, murine macrophages	Effects of EPs 7630 in in vitro models for intracellular infection with Leishmania parasites, an extracellular Leishmania growth assay, a fibroblast-virus protection assay (IFN activity), a fibroblast-lysis assay (TNF activity) and a biochemical assay for inorganic nitric oxides (iNO) were employed	TNF release, IFN induction, NO
Thäle et al. (2008) [60]	In vitro	Bone-marrow-derived mouse macrophages, Listeria monocytogenes	Effects of EPs 7630 on immunomodulators	NO, IL-1, IL-12, TNF-α, CD40, CD119
Trun et al. (2006) [64]	In vitro	Non-infected and Leishmania-infected RAW 264.7 cells	Effect of EPs 7630 on cytokine production	Gene expression of NO synthase and IL-1, IL-12, IL-18, TNF-α, IFN-α, and IFN-γ
Kolodziej and Kinderlen (2007) [69]	In vitro	Non-infected and Leishmania-infected murine macrophages	Antibacterial effects of EPs 7630 and their effects on non-specific immune functions	iNOS, IFN-α, IFN-γ, TNF-α, IL-1, IL-10, IL-12, and IL-18
Nöldner and Koch (2004) [55]	Animal study	NMRI mice	Effect of oral administration of a P. sidoides extract (100–400 mg/kg); 1 h later sickness behaviour was induced by intraperitoneal injection of LPS (400 μg/kg)	One hour later, behavioural effects were examined in the ‘light/dark box model’ by monitoring exploratory activity for 3 min
Nöldner and Schötz (2007) [56]	Animal study	NMRI mice	Effect of oral administration of a EPs 7630 extract (100–400 mg/kg) and subfractions; 1 h later sickness behaviour was induced by intraperitoneal injection of LPS (400 μg/kg)	Time spent in light compartment, number of changes
Walther et al. (2020) [50]	In vitro	MDCK and HeLa cells	Antiviral effects of P. sidoides against different types of rhinovirus and influenza virus	Cytotoxicity, viral plaque production, viral neuraminidase activity
Bao et al. (2015) [54]	Animal study	ICR mice SPF-class and guinea pigs	Antitussive, secretolytic, and anti-inflammatory effects of EPs 7630 were assessed in animal experiments following oral administration at human equivalent doses	Degree of tracheal and bronchial lesions, bronchosecretolytic (phenol red), concentrations of SOD and MDA in serum
Roth et al. (2019) [52]	In vitro	Human bronchial cells from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6)	The effect of EPs 7630 on human bronchial cells was assessed with western blot, immunofluorescence, and polymerase chain reaction	Protein expression, cell survival
Roth et al. (2021) [53]	In vitro	Human bronchial epithelial cells	The effect of EPs 7630 on human bronchial cells was assessed with western blot and immunofluorescence	Protein expression, intracellular signalling, antiviral effect
Witte et al. (2015) [63]	In vitro	Human monocytes (PBMCs), isolated from healthy donors	The effects of EPs 7630 on human monocytes was assessed by ELISA, western blot, and flow cytometry analyses	TNF-α, IL-6, and IL-10
Witte et al. (2020) [61]	In vitro	PBMCs	The effects of EPs 7630 on antimicrobial airway defense through monocytes	IL-22, IL-17, IFN-γ, IL-1, IL-23
Vimalanathan et al. (2017) [70]	In vitro	MDCK and BEAS-2B (human) cells. Influenza virus A and H. influenzae and S. aureus	Effect of an E. purpurea extract (EchinaforceTM) on H3N2-induced adhesion of live H. influenzae and S. aureus	Cytotoxicity, bacterial adhesion, expression of ICAM-1, fibronectin, PAFr, TLR4 and NFkB p65, IL-6 and IL-8
Fonseca et al. (2014) [80]	In vitro	Human Jurkat T-cells	Effect of different concentrations of E. purpurea extract (0, 10, 25, 100 and 250 μg/mL) on human T-cells was assessed	IL-2, IFN-γ, CD25 expression
Gertsch et al. (2004) [85]	In vitro	Human monocytes/macrophages	Echinacea alkylamides from EchinaforceTM	TNF-α protein and mRNA, cAMP, p38/MAPK, and JNK signaling, as well as NF-jB and ATF-2/CREB-1
Classen et al. (2006) [86]	In vitro	Mouse spleen cell cultures and mouse macrophages	Effects of different arabinogalactan-proteins from E. paalida were assessed	Proliferation, IgM production, induction of IL-6 and nitrite production
Keyhanmanesch et al. (2015) [93]	Animal study	Dunkin–Hartley guinea pigs	Intraperitoneal injection of different doses of α-hederin	IL-4, IFN-γ, and IL-17 levels in blood and histopathological evaluation of lungs and trachea
Sieben et al. (2009) [97]	In vitro	Human airway smooth muscle cells (HASM)	Cells were pre-treated with α-hederin, hederacoside, and hederagenin	β2 adrenergic receptor density, intracellular cAMP
Gepdiremen et al. (2005) [99]	Animal study	Wistar albino rats	Anti-inflammatory potential of a-hederin (monodesmoside) and hederasaponin-C from H. helix was assessed in carrageenan-induced acute paw edema in rats	Edema rate percentage
Wolf et al. (2011) [95]	In vitro	Bovine tracheal smooth muscle strips	Effects of the three main saponins of ivy, α-hederin, hederacoside C, and hederagenin, on the contraction and relaxation behaviour of isolated bovine tracheal smooth muscle strips by isometric tension measurements	Histamine-, methacholine-, and isoprenaline-induced relaxation of precontracted muscle strips
Hocauglu et al. (2012) [94]	Animal study	BALB/c mice	Mice were challenged with ovalbumin after which they received either a placebo, H. helix extract, or dexamethasone.	Goblet cell numbers, thickness of basement membrane, epithelium, and subepithelial smooth muscle layers
Saadat et al. (2015) [92]	Animal study	Dunkin–Hartley guinea pigs	Guinea pigs were sensitized with ovalbumin, after which a low (0.3 mg/kg) or high (3.0 mk/kg) dose of α-hederin was given	Tracheal response to methacholine, histamine and ovalbumin, white blood cell count
Shulte-Michels et al. (2016) [90]	In vitro	HEK293 cells	To assess the effect of H. helix extract on protein kinase A and G protein-coupled receptor kinases phosphorylation of β2 adrenergic receptors, an in-cell western was performed	Protein kinase A-mediated phosphorylation, G coupled receptor kinases phosphorylation
Greunke et al. (2015) [96]	In vitro	Human airway smooth muscle cells	The effect of an ivy leaf extract (EA 575) on human airway smooth muscle cells was assessed using live cell imaging, fluorescence correlation spectroscopy, and a cAMP assay	cAMP, internalization and binding of β-adrenergic receptors
Orhan et al. (2012) [88]	In vitro	S. pneumonia, S. pyogenes, S. aureus, S. epidermidis, M. tuberculosis, K. pneumoniae, H. influenzae, P. auruginosa, A. baumannii	Antibacterial effects of H. helix were assessed	DPPH inhibition, MIC
Schulte-Michels et al. (2019) [91]	In vitro	Mouse macrophages (J774.2), human embryonic kidney cells (HEK 293), acute monocytic leukemia cells (THP-1), and human lung epithelium-derived cells (A549)	Effect of EA 575 on transcriptional activity of NFkB was assessed	NFkB, IkBa and RelA, TNF-α
Schulte-Michels et al. (2016) [90]	In vitro	Murine macrophages (J774.2)	Different concentrations of EA 575 were tested for their effect on IL-6 release in macrophages	IL-6
Ünsal et al. (2010) [89]	Field study and in vitro study	S. aureus, S. epidermidis, E. coli, K. pneumoniae	During a three-month field study, 64 plant samples of plants that are traditionally used in common infections were collected and tested for antimicrobial activity	MIC
Acs et al. (2016) [108]	In vitro	Methicillin-resistant Staphylococcus aureus and the antibiotic-resistant Pseudomonas aeruginosa	With a tube dilution test, antimicrobial activity of thyme was assessed	MIC
Acs et al. (2018) [113]	In vitro	S. pneumoniae, S. mutans, S. pyogenes, H. influenzae, H. parainfluenzae, and M. catarrhalis	With broth microdilution test and vapor phase test, antimicrobial activity of thyme was assessed	MIC and MBC
Al-Bayati et al. (2008) [112]	In vitro	S. aureus, B. cereus, E. coli, P. vulgaris, P. mirabilis, S. typhi, S. typhimurium, K. pneumoniae, and P. aeruginosa	With microwell dilution method, the antimicrobial activity of T. vulgaris was assessed	MIC
Csikos et al. (2020) [117]	Animal study	C57BL/6J mice	Acute airway inflammation was induced in mice, essential oil of thyme was inhaled by one group of the animals	Airway function, hyperresponsiveness, and myeloperoxidase activity
Dahiya and Purkayastha (2012) [101]	In vitro	MDR clinical isolates of S. aureus (3 isolates), S. aureus (MRSA), Escherichia coli (3 isolates), K. pneumoniae (2 isolates), and P. mirabilis	With the agar well diffusion method, the antimicrobial activity of thyme was assessed	MIC
Fabio et al. (2007) [107]	In vitro	S. pyogenes, S. agalactiae, S. Pneumoniae, K. pneumoniae, H. influenzae, S. aureus, S. maltophilia	With the Kirby–Bauer paper method	Cytotoxicity, MIC, and MBC
Hammer et al. (1999) [111]	In vitro	Aer. Sobria, Candida albica, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa, S. enterica, S. marcescens, and S. aureu	With the agar dilution method and the broth dilution method, the antimicrobial activity of essential oil of T. vulgaris was assessed	MIC and MCC
Hoferl et al. (2009) [114]	In vitro	S. aureus, E. coli, P. aeruginosa, P. vulgaris, K. pneumoniae, and S. sp.	With agar diffusion disc method and agar dilution method, the antimicrobial activity of thyme was assessed	MIC and inhibition zone (IZ)
Inouye et al. (2001) [103]	In vitro	H. influenzae, S. aureus, S. pneumoniae, E. coli, and S. pyogenes	A minimum inhibitory dose was established to assess the antimicrobial activity of thyme	Minimum inhibitory dose (MID)
Iseppe et al. (2020) [104]	In vitro	E. coli, K. pneumoniae, P. aeruginosa	With agar diffusion disc method, the antimicrobial activity of essential oil of thyme was assessed	MIC
Javed et al. (2018) [100]	In vitro	S. aureus, P. aeruginosa, E. coli, P. vulgaris, K. pneumoniae	With the disk diffusion method, the antibacterial activity of T. vulgaris was assessed	MIC
Kwiatkowski et al. (2018) [109]	In vitro	K. pneumoniae	With broth microdilution method, the antimicrobial activity of essential oil of T. vulgaris was assessed	MIC, MBC
Lelesius et al. (2019) [116]	In vitro	Avian infectious bronchitis virus (IBV)/Vero Cells	Antiviral effects of T. vulgaris were assessed	Cytotoxicity, antiviral effect against IBV, and prior to infection in Vero cells
Man et al. (2016) [106]	In vitro	S. aureus, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa	Antibacterial effects of T. vulgaris were assessed	MIC, MBC
Marchese et al. (2016) [32]	Review	n.a.	Antibacterial and antifungal activities of thymol are researched in the literature	Chemistry, bioavailability, safety assessment, biological activity, antibacterial, and antifungal activity
Mohamed et al. (2019) [115]	In vitro	K. pneumoniae	Assessment of antibacterial effects of thymol, also in combination with ampicillin with disc diffusion assay and checkerboard assay	MIC, IZ
Mohammed et al. (2018) [105]	In vitro	K. pneumoniae	Assessment of antibacterial effects of essential oil of thyme, also in combination with ciprofloxacin with disc diffusion assay and checkerboard assay	MIC, MBC
Seibel et al. (2015) [120]	Animal study	Wistar rats	Bronchoalveolitis was induced in rats, which were then given different doses of Bronchipret (combination of ivy/primrose/thyme)	Granulocyte infiltration, effects on leukocytes, goblet cells in bronchial tissue, and leukotriene production and 5-LO enzyme activity
Van Vuuren et al. (2008) [121]	In vitro	S. aureus, K. pnuemoniae, C. albicans	Essential oil of T. vulgaris was assessed for antimicrobial activity, also in combination with conventional antimicrobials	MIC
Vazquez-Ucha et al. (2020) [110]	In vitro	A. baumannii and K. pneumoniae	Combined disk diffusion test and checkerboard assays were performed with the essential oil of T. zygis in combination with colistin	MIC
Wani et al. (2021) [102]	Review	n.a.	Literature review of antiviral potential of essential oils (including thyme)	Chemical composition, antiviral effects
Samuel and Priyadarshoni (2019) [75]	Review	n.a.	Literature review on biologic effects of Echinacea species	Active components, pharmacological actions, medicinal effects
Rondanelli et al. (2018) [76]	Review	n.a.	Literature review on the use of Echinacea in self-care for common colds	Effects on cellular immunity and adaptive immunity
Roxas and Jurenka (2007) [79]	Review	n.a.	Literature review on the use of Echinacea in treatment of the common cold	Incidence, signs and symptoms, potential complications, conventional treatment, alternative treatments
Barnes et al. (2005) [72]	Review	n.a.	Literature review on E. angustifolia, E. pallida, and E. purpurea	Chemistry, pharmacology, and clinical properties
Islam and Carter (2005) [87]	Review	n.a.	Literature review on the use of Echinacea in upper respiratory tract infections	Qualitative and quantitative properties, mechanism of action, clinical trials, and its effect on the immune system
Barret (2003) [73]	Review	n.a.	Literature review on the medicinal properties of Echinacea	Pharmacology, safety, contraindications, risk of adverse events, phytochemistry
Bash et al. (2005) [74]	Review	n.a.	Natural standard review on E. angustifolia, E. pallida, and E. purpurea	Toxicology, dosing, interactions, mechanism of action
Borchers et al. (2000) [77]	Review	n.a.	Literature review on Echinacea species	Anti-inflammatory activities, Echinacea species
Moyo and Van Staden (2014) [26]	Review	n.a.	Literature review on the uses and mechanism of action of P. sidoides	Phytochemistry, pharmacological properties, commercial potential, biotechnology application
Kolodziej et al. (2011) [67]	Review	n.a.	Literature review on the antimicrobial, antiviral, and immunomodulatory activities of P. sidoides	Respiratory tract related antibacterial activity, effect on mucociliary system, antiviral effects, immunomodulatory effects
Brendler et al. (2008) [68]	Review	n.a.	Literature review on pre-clinical and clinical studies of P. sidoides	Historical and commercial perspectives, scientific perspectives
Hossain et al. (2021) [35]	Review	n.a.	Literature review on A. paniculata	Phytochemistry, antimicrobial pharmacology, and clinical safety and efficacy
Jiang et al. (2021) [39]	Review	n.a.	Literature review on A. paniculata and andrographolide	Ethnopharmacology, phytochemicals, antiviral properties, toxicology
Kumar et al. (2021) [24]	Review	n.a.	Literature review on A. paniculata	Traditional uses, phytochemistry, pharmacology, and quality control
Okhuarobo et al. (2014) [47]	Review	n.a.	Literature review on A. paniculata	Phytochemistry and pharmacology