Complement Activation and Inhibition in Wound Healing

Table 2

An overview of complement inhibitors in extracts from plant species.

Plant L.	Part of plant (extract)	Mode of action	Beneficial effects	References
Achyrocline flaccida; (Yellow Marcela)	Aerial parts	CP inhibition.; IC50(CP)=23.5-88.9𝜇g/mL	Antispasmodic, antipyretic, antihelmintic, antibacterial, antiviral. Stimulant, emmenagogue, excitant.	[61]
Aloe vera	Leaves	AP activation, resulting in consumption of C3.	Antibacterial, antifungal, antiparasitic, antitumor, laxative. Used for seborrheic dermatitis, radiation dermatitis, psoriasis vulgaris, genital herpes, burn wounds, diabetes, HIV infection, ulcerative colitis, pressure ulcers, mucositis, aphthous stomatitis, acne vulgaris, lichen planus, frostbite, alopecia, systemic lupus erythematosus, arthritis, tic douloureux.	[62, 63]
Apeiba tibourbou; (Monkey comb)	Leaves	CP and AP inhibition.	Antispasmodic, mucilaginous, and pectoral properties. Used for rheumatism.	[64]
Artemisia species; (A. dracunculus, A. montana, A. princeps, A. rubripes, A. tripartita)	Leaves	CP inhibition.; IC50(CP)=54.3-64.2𝜇g/mL	Used for colic pain, vomiting, diarrhea, dysmenorrhea.	[65–68]
Ascophyllum nodosum; (Brown seaweed)	Leaves	CP inhibition. Fucoidan binds C1q and prevents the formation of active C1. It forms a complex with C4	Anti-inflammatory, antiangiogenic, anticoagulant, antiadhesive.	[69, 70]
Astronium urundeuva	Stem bark	CP and AP inhibition.; IC50 (CP) = 64 μg/mL; IC50 (AP) = 111 μg/mL	Used for wound healing, bone healing, inflamed sores, gastric ulcers, uterine hemorrhages, metrorragias, cervicitis.	[71]
Avicennia marina; (Evergreen shrub)	Stem bark	CP inhibition.; IC50 (CP) = 23–248 μg/mL	Antitumor, anti-inflammatory, antiviral. Used for skin diseases, wound healing, rheumatism, smallpox, ulcers, malaria.	[72]
Biophytum petersianum Klotsch	Aerial parts	CP inhibition.; IC50 (CP) ≤2–86 μg/mL	Used for wound healing, inflammation.	[65, 73]
Boswellia serrata; (Frankincense)	Oleogum resin	CP inhibition, it inhibits C3 convertase	Antihelminthic, antiseptic, haemostatic, analgesic, cardiotonic, diuretic, aphrodisiac, laxative. Used for Crohn’s disease, ulcerative colitis, bronchial asthma, rheumatoid arthritis, osteoarthritis, wound cleaning, reducing fat, diarrhea, improving menstruation.	[74, 75]
Bridelia ferruginea	Stem bark	CP and AP inhibition. Inhibition of C1 and terminal complex.	Used for rheumatism.	[76]
Cochlospermum vitifolium  (silk cotton tree)	Stem bark	CP and AP inhibition.; IC50 (CP) = 104 μg/mL; IC50 (AP) = 135 μg/mL	Used for diabetes, hepatobiliary and cardiovascular diseases, hypertension, pain, kidney diseases, ulcers.	[71, 77]
Croton draco	Latex	CP and AP inhibition.; IC50 (CP) = 430–590 μg/mL; IC50 (AP) = 680–930 μg/mL	Antibacterial, antitumor, antiviral. Used for wound healing, inflammation.	[78]
Entada africana	Roots	CP inhibition.; IC50 (CP) = 75–370 μg/mL	Hepatoprotective, haemostatic, antipyretic, antiseptic, diuretic, antigonococci, antisyphilitic, antiparasitic, abortifacient. Used for wound healing, malaria, respiratory diseases, psoriasis, rheumatism, cataract, dysentery.	[79]
Eugenia malaccensis; (Malay rose apple)	Stem bark	CP inhibition: IC50 (CP) = 12 μg/mL; AP was activated: 50 % activation at 6 μg/mL	Used for general debility, sore throat, wound healing, candidiasis, venereal diseases, tuberculosis, digestive tract disorders.	[80]
Eupatorium arnottianum	Aerial parts	CP and AP inhibition.; IC50 (CP) = 5.0–155.9 μg/mL; IC50 (AP) = 101.3 μg/mL	Antimicrobial, antiviral, antinociceptive. Used for gastric pain.	[61]
Eupatorium buniifolium	Aerial parts	CP inhibition.; IC50 (CP) = 44.1–66.7 μg/mL	Hepatoprotective, antiviral, antiseptic.	[61]
Euterpe precatoria; (Açai)	Roots	CP and AP inhibition.; IC50 (CP) = 105 μg/mL; IC50 (AP) = 147 μg/mL	Antioxidant. Used for muscular pain, sciatic pain, liver and kidney diseases, wound healing, skin ulcers, edema, inflammatory diseases.	[71]
Glycine max; (Soyabean)	Seeds	In vitro it inhibits synthesis and secretion of C2 and C4 by guinea pig peritoneal macrophages	Antioxidant, anti-inflammatory, antitumor, antioestrogenic, antifungal, insulinotropic. Used for atherosclerosis, skin whitening,	[81, 82]
Glycyrrhiza glabra  (Licorice)	Roots and rhizomes	Glycyrrhizin binds to C3a and C3. It induces conformational changes in C3 and it inhibits CP at the level of C2.	Anti-inflammatory, antiviral, antimicrobial, antioxidative, antitumor, immunomodulatory, hepatoprotective, cardioprotective, diuretic, anabolic, laxative, contraceptive. Used for wound healing, cystitis, diabetes, cough, stomachache, tuberculosis, nefrolitiasis, lung ailment, Addison’s disease, gastric ulcers, improvement of voice, improvement of male sexual function.	[83, 84]
Isopyrum thalictroides	Roots and aerial parts	CP inhibition. Ca^2+ and Mg^2+ dependent complement inhibition. It inhibits C1 formation.	Rheumatism, neuralgia, silicosis, malaria.	[81]
Jatropha multifida/Jatropha curcas  (Coral plant)	Latex	CP inhibition, mediated by Ca^2+ depletion	Used for infected wounds.	[81, 85]
Lithraea molleoides	Leaves	CP inhibition.; IC50 (CP) = 59.0–86.1 μg/mL	arthritic, haemostatic, diuretic, tonic. Used for respiratory diseases. It causes allergic contact dermatitis.	[61]
Opilia celtidifolia	Leaves	CP inhibition.; IC50 (CP) = 0.5–29 μg/mL	Haemostatic. Used for wound healing.	[73]
Piper kadsura; (Japanese pepper)	Stem bark	It inhibits C5a-induced chemotaxis and decreased the stimulated production of TNF-α and IL-1-β	Asthma, rheumatic arthritis	[86]
Phyllanthus sellowianus	Leaves and stems	CP and AP inhibition.; IC50 (CP) = 11.2–22.0 μg/mL; IC50 (AP) = 280.6 μg/mL	Hypoglycemic, diuretic, laxative, antiseptic, antinociceptic.	[61, 87]
Rosmarinus officinalis/Melissa officinalis  (Rosemary)	Leaves	CP and AP inhibition. It binds C3 and inhibits C5 convertase. C5a generation is decreased. IC50 (CP) = 2 μg/mL	Antispasmodic, choleretic, hepatoprotective, anti-inflammatory, antitumor, antioxidant. Used for renal colic pain, dysmenorrhea, respiratory disorder (bronchial asthma), stimulation of hair growth, relaxation of smooth muscles of trachea and intestine, peptic ulcers, atherosclerosis, ischaemic heart disease, cataract, improvement of sperm motility.	[81, 88, 89]
Trichilia emetica; (Natal mahogany)	Leaves	CP inhibition.; IC50 (CP) = <15–62.5 μg/mL	Antipyretic, antiepileptic, antigonococci, antisyphilitic, anti-parasitic. Used for wound healing, dysmenorrhea, asthma, vomiting, hepatitis, improvement of fertility (women), gastric diseases, malaria, hypertension, rheumatism, lumbago.	[90]
Triplaris americana; (Ant tree)	Stem bark	CP and AP inhibition.; IC50 (CP) = 74 μg/mL; IC50 (AP) = 89 μg/mL	Antioxidant, parturifacient. Used for metrorragias, diarrhea, stomachache, intestinal worms, leishmaniasis, skin ulcers.	[71]
Ulex europaeus  (Common gorse)	Seeds	It attenuates MBL binding on human endothelial cells and inhibited C3 deposition. The dcreased LP activation resulted in less complement-dependent neutrophil chemotaxis.; IC50 = 10 pmol/L	None.	[91]
Uncaria tomentosa  (Cat’s claw)	Stem bark	CP and AP inhibition.; IC50 (CP) = 124 μg/mL; IC50 (AP) = 151 μg/mL	inflammatory, antiviral, immunostimulating, antimutagenic, antioxidant. Used for gastritis, dermic and urogenital inflammations, asthma, rheumatism, irregular menstruation, digestive, liver and kidney diseases, adjuvant therapy for breast cancer.	[71, 92]

CP: classical pathway; AP: alternative pathway; LP: Lectin Pathway; IC₅₀: concentration required for 50% complement inhibition. Most of these complement inhibition tests were performed using complement haemolytic activity assays. Compounds in these plant species inhibiting the complement system are e.g. flavonoids, glucosides, polysaccharides, terpenes, iridoids, polymers, peptides, alkaloids, and oils [81]. Other complement inhibitors from plants are found in Acanthus ilicifolius[72], Atractylodes lancea[73], Angelica acutiloba [73, 81, 93], Azadirachta indica [81], Bupleurum falcatum [94], Cedrela lilloi [81], Centaurium spicatum [81], Cochlospermum tinctorium[95], Crataegus sinaica [81], Crataeva nurvala [81], Curcuma longa [96], Dendropanax morbifera Leveille [97], Glinus oppositifolius [79], Juglans mandshurica [98], Ligularia taquetii [99], Litsea japonica [100], Ligustrum vulgare [81], Lithospermum euchromum [81], Magnolia fargesii [101], Melothria maderaspatana [102], Morinda morindoides [81], Olea europaea [81], Osbeckia octandra [102], Ocimum basilicum [66], Osbeckia aspera [81], Panax ginseng [103], Paulownia tomentosa var. tomentosa [104], Persicaria lapathifolia [81], Petasites hybridus [81], Phillyrea latifolia [81], Phyllanthus debilis [102], Picria fel-terrae [105], Plantago major [81], Sorghum bicolor [106], Terminalia amazonia [71], Thymus vulgaris [66], Tinospora cordifolia [81], Trichilia elegans [90], Trichilia glabra [81, 90], Vernonia Kotschyana [72, 73, 95], Wedelia chinensis [107], and Woodfoidra fruticosa [81].