Table 2.
Natural compounds with anti-inflammatory activity obtained by SFE.
| Natural source | Extraction Conditions | Compounds | Analytical characterization | Type of study | Remarks | Ref. |
|---|---|---|---|---|---|---|
| Aloysia gratissima (leaves) | 20 MPa, 60°C for 120 min, 2 g/min | Terpenes (guaiol, pinocamphone, caryophyllene oxide and spathulenol) | GC-MS | In vivo | Significant reduction of mice paw edema up to 3 h after injury induction (10 mg/kg) | [50] |
| Bidens pilosa (aerial parts) | 30 MPa, 40°C, 5 L/min | Fatty acids (palmitic, oleic, linoleic, linolenic) | GC-MS | In vivo | Effective in preventing or treating intestinal inflammation in rats (25–100 mg/kg) | [29] |
| Carvi seeds (Carum carvi) | 20 MPa, 40°C, 14 mL/min for 180 min | Fatty acids, sterols (â-Sitosterol) and polyphenols | GC-FID GC-MS |
In vitro | Strong anti-inflammatory activity compared to conventional extraction. IC50 = 24. μg/mL | [59] |
| 9 MPa and 40°C | Terpenes (limonene, carvone) | GC-FID GC-MS |
In vivo | Gastroprotective effects in rats (300 mg/kg) | [58] | |
| Arctium lappa (leaves) | 20 MPa, 60°C for 40 min | Terpenes (lupeol acetate, phytol and α-amyrin) | GC-MS | In vitro | Co-solvent improved the extraction yield, as well as the inhibitory activity. IC50 = 74.69 μg/mL | [51] |
| Turmeric (Curcuma sp.) | 40 MPa, 45°C, 2 mL/min, 20% isopropanol for 60 min | Terpenes (Isoborneol, curdione, vellaral, procurcumadiol, germacrone) | LC-Q-TOF-MS, ESI(+) GC-Q-TOF-MS, EI |
In vitro | Co-solvent increased lipoxygenase inhibition in 62.5–86.55% | [24] |
| 35 MPa, 65°C, 2 mL/min for 150 min, 30% EtOH | Terpenes (curcuminoids) and phenolics | LC-Q-TOF-MS, ESI(+) | In vivo | The specie with higher amount of curcuminoids showed lower activity due to limited bioavailability; 1 g/kg reduced 70% of the inflammation in rats | [25] | |
| 40 MPa, 50°C, 3.2 L/min | Terpene (xanthorrhizol) | – | In vivo | Attenuation of periodontal inflammation in rats (30–100 mg/kg/day) | [26] | |
| Neem leaves (Azadirachta indica) | Not informed (Nisarga Ltd., Satara, Maharashtra, India) | Terpenes | – | In vitro | Reduced inflammation associated with colon cancer | [70] |
| – | In vivo | Decreased the oral cancer cell proliferation in rats (200 mg/kg) | [71] | |||
| Angelica sinensis and Zingiber officinal (roots) (7:4 w/w) | 8 MPa, 55°C, 25 L/h, | Phthalide (ligustilide) Phenolic (6-gingerol) |
GC-MS HPLC-UV |
In vivo | Ameliorated colitis symptoms by decreasing oxidative stress and suppressing inflammatory mediators in rats (60 mg/kg) | [31] |
| Ginger (Zingiber officinale) | 22.7 MPa, 50°C for 3 h | Not identified | – | In vivo | Rat paw edema decreased by 24.66% (25 mg/kg) | [72] |
| Pepper (fruits) | 20 MPa, 50°C, for 1 h | Amide, terpenes, olefins and ester | HPLC-PDA, UV GC-TQ-MS |
In vitro | Anti-inflammatory and antitumor effects were better than the reflux and ultrasonic ethanol extracts. IC50 = 4.19 μg/mL | [67] |
| 10–30 MPa, 40°C, 2 L/min for 60 min | Alkaloid (Piperine) | HPLC-UV | In vitro | Activities comparable with ascorbic acid and diclofenac sodium (200 μg g/mL) | [73] | |
| White pepper, long pepper, cinnamon, saffron and myrrh mixture | 30 MPa, 50°C for 2 h | Terpenes (β-selinene, aromadendrene, β-elemene, cis-piperitol) | GC-MS | In vivo | Inhibition of peripheral inflammatory pain in rats (62.5–1000 mg/kg) | [45] |
| Valeriana glechomifolia (aerial and subterraneous parts) | 9 MPa, 40°C, 6.67 × 10−4 kg/s. | Terpenes (valtrate, acevaltrate) | HPLC 1H and13C NMR |
In vivo | The activity was comparable or better than the positive control in the treatment of inflammation induced in rats (1–30 mg/kg) | [74] |
| Achillea millefolium (leaves) | Fractionation of ultrasound-assisted extract – 15 MPa, 40°C | Terpenes (camphor, artemisia ketone and borneol) | HPLC-QTOF-MS, ESI (−) GC-MS |
In vitro | The higher the concentration of terpenes, the greater the anti-inflammatory activity. | [44] |
| Leptocarpha rivularis (stalks) | 40 MPa, 60°C, 3.7–4.6 L/min | Terpene (caryophyllene oxide) Phenolics (quercetin, kaempferol and resveratrol) | HPLC-DAD GC-FID |
In vitro | The highest activity was obtained with the presence of co-solvent. IC50 = 2.7 mg/mL α-glucosidase; IC50 = 15.1 mg/mL α-amylase | [34] |
| Acanthus ilicifolius Linn (leaves) | Not informed | Alkaloid (2-benzoxazolinone) | HPTLC-UV | In vivo | Oral safety and anti-inflammatory activity were assayed (>2000 mg/kg) | [66] |
| Leaves and stems of cipó-pucá | 40 MPa, 40°C, and 10% EtOH, 4.52 g/min | Terpenes, phenolic compounds, flavonoid | HPTLC-UV | In vivo | Anti-inflammatory response in the central nervous system of rats | [65] |
| Rice bran | 45 MPa, 60°C | Terpenes (γ-oryzanol, tocotrienol and tocopherol | HPLC-UV | In vitro | Potent activity comparable to the positive control in the treatment of inflammatory bowel diseases. IC50 = 15–28 μg/mL | [32] |
| Apium graveolens (seeds) | Separex®, Champigneulles, France | Terpene (Senkyunolide) | UPLC-UV | In vivo | Reduced dandruff formation and soothes the human scalp | [60] |
| Ligusticum chuanxiong | 35 MPa, 60°C, 20 L/h for 3 h | Terpene (ligustilide and senkyunolide) | GC-MS | In vivo | Mitigated liver and kidney injury in d-galactose-treated mice | [52] |
| Physalis angulata (aerial parts) | 30 MPa, 40°C, 5 L/min for 150 min | Phytosterols | – | In vivo | Modulation of pathways and mediators of the intestinal inflammatory response in rats (25–100 mg/kg) | [30] |
| Pinus densiflora (needle) | 30 MPa, 60°C, for 2 h. CO2 and ethanol flow rate of 140 and 10 mL/min | Not identified | – | In vitro | Inhibitory effect on the expression of pro-inflammatory mediators | [75] |
| Perilla frutescens (leaves) | 40 MPa, 50°C, 60 mL/min for 3 h | Terpene (isoegomaketone-IK) | HPLC-UV | In vitro | SFE exhibited approximately 10-fold higher IK content and much stronger anti-inflammatory activity compared with ethanol extract | [61] |
| Brown Seaweed (Undaria pinnatifida) | 20 MPa, 45°C, 250 mL/min for 30 min | Fatty acid (palmitic acid) | GC-MS | In vivo | Active against mouse ear inflammation. IC50 = 87 μg/ear | [57] |
| Lonicera japonica (flower buds) | 15, 25 and 35 MPa at 45°C for 2 h | Polyphenols (chlorogenic acid and luteolin-7-O-glucoside) | UPLC-ESI-MS/MS GC-MS |
In vitro | SFE extracts showed anti-inflammatory activity superior to water and ethanol. IC50 = 100 μg/mL | [35] |
| Litsea japonica (fruit) | 30 MPa, 60°C, 60 ml/min for 180 min | Flavonoids and lactones | HPLC-UV | In vitro | Modulation of expression of pro-inflammatory mediators | [62] |
| Ishige okamurae (alga) | 40 MPa, 40°C for 2 h | Fatty acids | GC-FID | In vitro | Anti-inflammatory response in macrophage cells | [76] |
| Ginger (Zingiber officinale) | 30 MPa, 30°C 1.42 × 10−4 kg/s | Terpenes | GC-MS | In vitro | Inhibition of pro- inflammatory cytokine production | [53] |
| Rosemary (Rosmarinus officinalis) | 25 MPa, 40°C, 1.13 × 10−4 kg/s | Terpenes | GC-M | In vitro | Inhibition of pro- inflammatory cytokine production | [53] |
| Thunbergia laurifolia (leaves) | Not identified | Not identified | – | In vivo | Acceleration of burn wound healing in rats treated with gel with 10% extract | [77] |
| Copaíba leaves (Copaifera sp.) | 20 MPa, 60°C, 8.33 × 10−5 kg/s for 2 h | Not identified | – | In vivo | Neuroprotective effects in stroke induced in rat brains (50 mg/kg) | [78] |
| Ledum palustre (aerial parts) | 9 MPa and 40°C | Terpenes (palustrol, ledol, ascaridole) | GC-MS | In vivo | Inhibition of the hind paw edema in rats (50–80%) | [56] |
| Marjoram (Origanum majorana) | 30 MPa, 40°C, 60 g/min | Terpenes (sabinene hydrate and terpineol) | GC-MS | In vitro | Inhibition of pro-inflammatory cytokine secretion and gene expression (10 μg/mL) | [54] |
| Sweet basil (Ocimun basilicum) | 30 MPa, 40°C, 60 g/min | Terpenes (Linalool and eugenol) | GC-MS | In vitro | Inhibition of pro-inflammatory cytokine secretion and gene expression (10 μg/mL) | |
| Sage (Salvia officinalis) | 30 MPa, 40°C, 50 g/min | Terpenes (camphor, borneol, 1,8 cineole | GC-MS | In vitro | Suppression of pro-inflammatory cytokine production (30 μg/mL) | [55] |
| Seabuckthorn leaves (Hippophae rhamnoides) | 35 MPa, 60°C, 25% EtOH | Flavonoids (myricetin, isorhamnetin) | HPLC-UV HPTLC |
In vivo | Reduction of inflammation in response to tetanus and diphtheria toxoids in rats (100 μg/rat) | [39] |
| 20 MPa, 50°C, 25% EtOH | Flavonoid (isorhamnetin) | HPLC-UV | In vivo | Attenuation of endotoxin-induced sepsis in rats (27 μg/kg) | [63] | |
| 20 MPa, 50°C, 25% EtOH | Flavonoid (isorhamnetin) | HPLC-UV | In vivo | Significant reduction in the induced-arthritis inflammation (270 μg/kg) | [64] | |
| Morus alba (Branches) | Not identified | Phenolic (oxyresveratrol) | GC-MS | In vitro | Inhibition of pro-inflammatory pathways | [38] |
| Chrysanthemum indicum (flowers) | 25 MPa, 45°C, 20 L/h for 4 h | Fatty acids (glyceryl 2-linoleate, glycidyl palmitate, ethyl linoleate and ethyl oleate); Terpenes (camphor, (isoborneol, eucalyptol caryophyllene oxide); | GC-MS HPLC-UV |
In vivo | Mitigation of liver and brain injury in rats (100–300 mg/kg) | [28] |
| Institute of New Drug Research & Development Guangzhou University of Chinese Medicine | Terpenes (camphor, borneol, eucalyptol, thymol, curcumene) | GC-MS HPLC-UV |
In vivo | Attenuation of inflammation pathways associated with tumor activities | [8] | |
| In vivo | Attenuation of inflammation induced by acute lung injury in mice (120 mg/kg) | [27] | ||||
| 25 MPa, 45°C, 20 L/h for 4 h | Terpenes (eucalyptol, bornyl acetate, caryophyllen, caryophyllene oxide); Phenolics (thymol, bisabolol oxide); Alkenes (curcumene, verbenol) |
GC-MS HPLC-UV |
In vivo | Attenuation of edema induced in rats (40 mg/kg) | [68] | |
| 25 MPa, 45°C for 3h | Not identified | – | In vivo | The extract was mixed in a 3:3:1 (w/w) ratio with patchouli oil and turmeric oil. Significant suppression of edema in rats (170 mg/kg) | [79] | |
| Spinach leaves | 35 MPa, 40°C, 60 g/min for 6 h | Carotenoids (lutein and β-carotene) | HPLC-UV | In vitro | SFE extract showed higher activity than PLE extract | [36] |
EtOH: ethanol; ESI: Electrospray ionization source; EI: Electronic impact ionization source, HPTLC: High-performance thin-layer chromatography.