Table Info

Table 2.

Pharmacological activity of phytoconstituents of FA

Phytoconstituent	Pharmacological activity/dosing	Mechanism	References
β-Lapachone, lapachol	Antitumor activity (compared to 75% of the animals that received β-lapachone 50 mg/kg IT and 100% of the animals that received β-lapachone 75 mg/kg IT)	The potent antipancreatic cancer drug-lapachone is more bioavailable, effective, and toxic when it is complexed with HPβ-CD.	[52]
Lapachol		Lapachol exhibits relatively substantial action when administered orally, intraperitoneally, subcutaneously, intramuscularly, or in combination against Walker 256 carcinosarcoma.	[53]
Naphthoquinone derivatives		A promising foundation for their potential use in the treatment of prostate cancer comes from the antitumoral activity of certain of the produced naphthoquinone derivatives.	[54]
Lapachol (2-hydroxy-3-(3-methyl-2-butenyl)- 1,4-naphthoquinone derivative		When lapachol is acetylglucosylated, a substance that increases lapachol activity starts to work against mouse lymphocytic leukemia P-388.	[55]
β-Lapachone, lapachol		β-Lapachone, an O-naphthoquinone derived from lapachol, is now being tested for use against Trypanosome cruzi, cancer, viruses, and bacteria.	[56]
β-Lapachone		Changes in morphology in PC3 cells after single and combined-treatment with β-lapachone and genistein isoflavone, including cell shrinkage and chromatin condensation.	[57]
β-Lapachone		Regardless of the tumor’s sensitivity to hormones, the chemotherapy for prostate cancer provided by the combination of β-lapachone and genistein will be effective.	[58]
β-Lapachone		β-Lapachone’s ability to induce a seemingly unique, calpain-like-mediated apoptotic cell death could be beneficial in the treatment of breast and prostate cancer.	[59]
β-Lapachone	Antibacterial and antifungal activity [inhibitory activity was found against Microsporum gypsum (50 μg/mL) as compared to standard salicylic acid (200 μg/mL)]	Even when the results were converted into mg/mL, β-lapachone outperformed ketoconazole in terms of effectiveness. If the toxicity is confirmed, many medical applications may be avoided. However, the impact they have on bacteria and fungi may be useful for protecting plants.	[52, 60]
β-Lapachone, lapachol	Anti-plasmodial activity (IC₅₀< 1.25 μmol/L to 10 μmol/L)	Natural lapachol and β-lapachone were evaluated on the cultivation of the F32 strain of Plasmodium falciparum, and certain derivatives showed promising in vitro activity (IC₅₀ < 10 μmol/L).	[61]
Naphthoquinone derivatives	Mollusicidal activity (LC₅₀ values is 3.1 μg/mL)	The lipophilic feature of the amino alkyl side chain improved the molluscicidal action of amino derivatives of lapachol. These compounds have low to medium LC₅₀ values, with the most potent derivative in the series having a 3.1 μg/mL value.	[62]
Hydroxynaphthoquinones derivatives	Mollusicidal activity (LC₅₀ values is 3.1 μg/mL)	However, other aspects must also be taken into account. The trend in hydroxynaphthoquinones derivatives shows that bioreduction may play a significant role in the molluscicidal activity of these compounds.	[63]
Lapachol, isolapachol, and dihydrolapachol	Antileishmanial activity [minimum lethal concentration (MLC) 100 μg/mL and minimum inhibitory concentration (MIC), 50 μg/mL]	Hydroxyquinone derivative has shown activity against Leishmania amazonensis and Leishmania braziliensis in vitro and in vivo, as well as being a very promising antileishmanial medication.	[64, 65]
1,2-Naphthoquinones, lapachol, β-lapachone	Antimalarial activity (KD50 57.51 and KD90 98.32 was determined by probit analysis, while mortality value after 24 h was 10.6% ± 0.2%)	Utilizing isolates of parasites with varying susceptibilities to chloroquine and/or mefloquine, benzo[a]phenazines produced from 1,2-naphthoquinone, lapachol, β-lapachone, and other derivatives have been investigated for their antimalarial efficacy against Plasmodium falciparum in vitro.	[66, 67]
1,4-Naphthoquinones and 1,2-naphthoquinones derivatives	Antiviral activity	Epstein-Barr virus early antigen (EBV-EA) activation caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined for the inhibitory effects of many derivatives made from the naphthoquinone lapachol and TPA.	[68]
Friedelin	Antiulcerogenic activity (doses of friedelin 20, 25, 30, 35, 40 and 45 mg/kg)	These results suggested that the anti-ulcer potential of friedelin, which may involve antioxidants, endogenous prostaglandins, nitric oxide, K⁺ATP channel opening, maintaining the balance between pro and anti-inflammatory cytokines, antiapoptotic function, could be a new useful natural gastroprotective tool against a gastric ulcer in the rat model.	[69]
Friedelin	Anti-diarrhoeal activity [friedelin (20 mg/kg) showed significant (P < 0.0001)]	The overall findings revealed that friedelin’s anti-diarrheal activity may be related to its anti-secretory and anti-motility properties, providing support for the traditional assertion.	[70]
Friedelin	Anti-inflammatory, analgesic, and antipyretic activity (40 mg/kg dose of friedelin with a significance value of P < 0.05)	Friedelin had substantial anti-inflammatory, analgesic, and antipyretic properties in vivo. Friedelin’s major mode of action may be to inhibit the synthesis or release of inflammatory mediators.	[71]
Friedelin	Hypolipidemic activity [friedelin (50 mg/kg and 70 mg/kg) caused a lowering of lipid levels in plasma and the liver showed a significant (P < 0.01)]	The current investigation found that friedelin had the greatest efficacy in decreasing increased cholesterol levels in Triton WR-1339 and high-fat diet-induced hyperlipidemic rats.	[72]
Friedelin	Hepatoprotective activity [friedelin at 40 mg/kg (IC₅₀ 21.1 mmol/L), hydroxyl (IC₅₀ 19.8 mmol/L), nitric oxide (IC₅₀ 22.1 mmol/L) and superoxide (IC₅₀ 21.9 mmol/L) radicals]	Friedelin demonstrated effective antioxidant, free radical scavenging, and liver protecting properties in both in vitro and in vivo investigations. It may be useful in avoiding or reducing the progression of several oxidative stress-related illnesses.	[73]
OA and UA	Osteoprotective effect [medium Ca diet (MCD, 0.6% Ca), high Ca diet (HCD, 1.2% Ca), MCD + FLL (700 mg/kg per day), MCD + OA (23.6 mg/kg per day) + UA (8.6 mg/kg per day)]	This study offers proof that OA + UA may be employed as a cutting-edge, orally administered treatment medication for osteoporosis management and prevention.	[74]
OA		In mature C57BL/6 ovariectomized (OVX) mice, OA dramatically enhanced bone mineral density, improved micro-architectural characteristics, decreased urine Ca excretion, and elevated 1,25(OH)₂D₃ and renal CYP27B1 messenger RNA (mRNA) expression. OA also enhanced bone characteristics.	[75]
Oleanolic and UAs	Antibacterial activity [gram-positive bacteria: 4 mg/L against Enterococcus faecalis, and 8 mg/L against both strains of S. aureus, for UA; 8 mg/L against Enterococcus faecalis, 32 mg/L S. aureus American type culture collection (ATCC) 29213 and 64 mg/L against S. aureus ATCC 25923, for OA. Both compounds, UA and OA, were devoid of activity against gram-negative bacteria (≥ 256 mg/L, for E. coli and Pseudomonas aeruginosa)]	Numerous bacterial species, particularly gram-positive ones like mycobacteria, are susceptible to the effects of OA and UA. They prevent bacterial survival and growth, and a wide range of MICs values are available.	[76]
Oleanolic, ursolic and BA		When it comes to the treatment of bacterial infections, UA, OA, and BA establish the genuine value of such ethnopharmacology approaches by determining antibacterial activity as well as cellular impact (i.e., viability and cytotoxicity).	[77]
Oleanolic and UA	Antimutagenic effect [UA (80 mg/kg b.w.); OA (80 mg/kg b.w.) and a mixture of UA and OA (80 mg/kg b.w.)]	Under the experimental conditions utilized in this study, UA and OA reduced doxorubicin (DXR) clastogenicity in mouse peripheral blood and bone marrow cells. It has promising candidates for the prevention of cancer and other disorders.	[78]
UA		UA has demonstrated that its in vitro chemopreventive properties can shield DNA from both endogenous and induced DNA damage in both types of cells.	[79]
UA	Anti-neoplastic activity (20–120 μmol/L of UA for HT-29 cells)	As a strong anti-cancer drug for colorectal cancer therapy, usolic acid causes apoptosis in colorectal cancer cells by upregulating micro (miR)-4500 and inhibiting signal transducer and activator of transcription 3 (STAT3) activation.	[80]
UA		Due to its capacity to influence various intracellular signal STAT3, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 pathways targets, UA has a wide variety of actions. Both in vivo and in vitro, UA dramatically reduces the activation of several CRC-related signaling pathways.	[81]
Glycyrrhetic, oleanolic, and UAs	Anti-ulcerogenic activity (HCT15 cells treated with UA 30 μmol/L and OA 60 μmol/L)	Pentacyclic triterpene derivatives (Gl, OA, UA) with anti-ulcer action have advanced to the point where a number of novel substances are available that are potenter than carbenoxolone, essentially devoid of mineralocorticoid activity, and possibly non-toxic.	[82]
OA and UA	Hepatoprotective activity [OA and UA with IC₅₀ (K_i) values of 143.5 (74.2) μmol/L and 78.9 (41.0) μmol/L)]	The current investigation shows that UA inhibits CYP2C19 in human liver microsomes and that OA has an inhibitory impact on CYP1A2 and CYP3A4.	[83]
UA and asiatic acid		The processes by which UA and asiatic acid have demonstrated protective effects may be linked to direct protection of mitochondria and hepatocytes as well as the potent scavenging of reactive oxygen species (ROS), which may indirectly benefit mitochondria.	[84]
BS	Anti-inflammatory activity [BS (0.1–200 μmol/L)]	BS strongly reduces vascular adhesion molecule 1 and intracellular adhesion molecule 1 expression in TNF-α-stimulated HAEC, as well as U937 cell binding to TNF-α-stimulated HAEC and attenuates nuclear factor-kB p65 phosphorylation.	[85]
BS	Anti-diabetic activity [BS treatment (10, 15 and 20 mg/kg, p.o.)]	In STZ-induced diabetes, BS protects serum and pancreatic tissue, as well as antioxidant status.	[86]
BS		The anti-hyperglycemic action of the BS extract may be attributed to both protection against oxidative damage in alloxanized diabetes and an increase in peripheral glucose consumption.	[87]

p.o.: oral; TNF-α: tumor necrosis factor α; K_i: inhibition constant; CRC: colorectal carcinoma; b.w.: body weight; BA: betulinic acid; Ca: calcium; FLL: fructus ligustri lucidi; IT: intratumoral; HPβ-CD: hydroxypropyl-β-cyclodextrine; LC₅₀: lethal concentration

Declarations

Author contributions

TY and SKM: Writing-original draft. TY: Writing-review & editing. MSA and AW contributed to various areas of the manuscript and critically evaluated it. Each author reviewed and approved the version that was submitted after helping to revise the document.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright

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