Potential Efficacy of Herbal Medicine-Derived Carbon Dots in the Treatment of Diseases: From Mechanism to Clinic

Figures & data

Table 1 The Comparative Summary of Synthesis Strategies for HM-CDs

Method	Advantages	Disadvantages	Influencing Factors	Recommendations	Applicability
Hydrothermal method	(1) One of the most mature single-step synthesis techniques. (2) Straightforward preparation procedures, minimal experimental needs, and low cost. (3) Maximized safety and reduced toxicity. (4) Simplicity to achieve superior quantum yields.	Long reaction time	Reaction temperature and time	Reaction temperature and time are sufficiently considered and verified.	Most fruits, juices, peels, and vegetables
Pyrolysis method	(1) Simple, convenient, and low toxicity. (2) Controllable temperature and time.	(1) Low quantum yield. (2) High equipment requirements.	(1) Pyrolysis temperature and time. (2) pH value of the reaction system.	Improve the performance of pyrolysis equipment.	Most charcoal-based medicines
Microwave method	(1) Simple equipment and operation, energy-saving and efficient, which can be promoted in production. (2) Controllable temperature and time. (3) High precision and low pollution. (4) Shorten the reaction time and considerably improve the yield and purity.	Uneven particle size distribution of CDs	Temperature and time	Regulation of particle size by sonication, gel electrophoresis, column chromatography, and other treatments.	For light-textured charcoal herbs
Solvothermal method	(1) Environmentally friendly and lower energy consumption. (2) No need for expensive heating equipment, low cost. (3) No need for long-time high-temperature heating, easy operation, and simple equipment.	Large particle size of CDs	The choice of solvent is the key to determining the performance of HM-CDs.	–	Multiple carbon precursors

Figure 1 Preparation methods of HM-CDs. (A) hydrothermal synthesis process; (B) pyrolysis synthesis process; (C) microwave carbonization synthesis process.

Table 2 HM-CDs Synthesized by Microwave Carbonization

Source	Reaction Temperature (°C)	Reaction Time	Excitation Spectra (nm)	Emission Spectra (nm)	Average Particle Size (nm)	Quantum Yield (%)	Rf
Mentha canadensis Linnaeus	960	4–7 min	340	436	2.43	17	[41]
Bombyx mori L.	210	0.75 h	350	440	19	46	[42]
Zingiberis rhizome and Alpinia officinarum	450	5–40 min	--	--	10	--	[43]
Ginkgo biloba Linn.	800	5–15 min	440	550	2.82	0.65	[18]
Panax ginseng	700	0.5 h	380	500	2	8	[44]
Talinum paniculatum (Jacq.) Gaertn.	700	0.5 h	380	470	2	--	[45]
Rose flowers	--	--	390	435	4–6	13.45	[46]
Ginkgo fruits	800	5–15 min	380	--	2.82	0.65	[18]
Orange peel	900	1 min	420	522	4.2	16.20	[40]

Figure 2 HM-CDs significantly improved blood-brain barrier (BBB) permeability. HM-CD-1 has an ultra-tiny size and abundance surface functional groups. The covalent binding of HM-CD-2 to the drug facilitates passive transport of the drug. HM-CD-3 has a strong affinity for the BBB endothelial cell membrane.

Figure 3 The current application of HM-CDs in disease treatment, including hematological system (hemostasis, hypoglycemic, and blood enrichment), bacterial infection, inflammation-related diseases (arthritis, epidermal inflammation, allergic inflammation, and organ damage inflammation), anticancer, diseases related to oxidative stress, other disease areas (menopausal syndrome, anxiolytic).

Table 3 HM-CDs as Potential Therapeutic Agents for Hematological Disorders

Pharmacological Effects	Source	Mechanism of Action	References
Hemostasis	Cirsium Setosum Carbonisata (CSC)	The PT decreased, and the FIB content increased.	[79]
	Schizonepetae Herba Carbonisata (SHC)		[60]
	Junci Medulla Carbonisata (JMC)		[80]
	Ptollen Typhae Carbonisata (PTC)	The APTT decreased, and the FIB and PLT content increased.	[78]
	Egg yolk oil (EYO)		[81]
	Typha angustifolia L.	The PT values and APTT values were shortened.	[82]
	Dry rhizome node of Nelumbo nucifera Gaertn.
	Dry rhizome node of Cirsium japonicum Fisch. ex DC.
	Healthy human hair
	Cirsii Japonici Herba Carbonisata (CJHC)	The FIB levels and PLT amount increased.	[77]
	Phellodendri Cortex Carbonisata (PCC)		[83]
	Radix Puerariae Carbonisata (RPC)	Improved bioavailability	[84]
	Schizonepetae Spica Carbonisata (SSC)	Inhibiting the haemorrhagic activity of D. acutus venom via PLT elevation	[12]
Glucose-lowering effect	Jiaosanxian	--	[[85]
Blood enrichment	Jujube	Regulation of the hypoxia response pathway and up-regulation of STAT5 phosphorylation levels to specifically enhance the proliferation of erythroid cells	[86]

Figure 4 Mechanisms of hemostasis. Under the synergistic effect of platelet activation, coagulation factors undergo a complex coagulation cascade to produce thrombin (also known as activated factor II (IIa)), which converts fibrinogen (also known as factor (I) in adjacent plasma into fibrin (also known as factor Ia). The interwoven fibrin makes platelets clot and blood cells tangle into thrombi at the bleeding site. The coagulation cascade includes extrinsic and intrinsic pathways. The extrinsic pathway is initiated by the exposure of blood to tissue factor (TF) following tissue damage and eventually leads to the activation of factor X into factor Xa. For the intrinsic pathway, factor XII is activated when blood contacts a negatively charged surface, resulting in the downstream proteolytic activation of other coagulation factors until factor X is activated into factor Xa. The two pathways converge into a common pathway through factor Xa. Factor Xa cleaves prothrombin (also known as factor II) into thrombin in the presence of phospholipids and Ca²⁺, and thrombin converts fibrinogen into fibrin to achieve the main goal of haemostasis.

Abbreviations: HMWK, high molecular weight kininogen; KLK, kallikrein; PKLK, prekallikrein.

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