Hyaluronidase

Hyaluronidase is a natural enzyme that can degrade hyaluronic acid and has high specificity and hydrolytic activity^[1]. The mechanism of action of hyaluronidase is mainly to reduce the viscosity and molecular weight of hyaluronic acid by cutting the β-1,4-glucosidic bond of hyaluronic acid^[2]. In humans, six different hyaluronidases have been identified, HYAL 1-4, HYAL-P1 and PH-20, of which PH-20 has the strongest biological activity^[3]. Hyaluronidase is often used to improve the tissue permeability of drugs, promote drug absorption, and can also reverse adverse reactions caused by hyaluronic acid fillers^[4].

In vitro, hyaluronidase (100mU/ml) treatment of astrocytes that knocked down CD44 expression for 24 hours enhanced the activity of Rac1, causing the cells to become "star-like" morphology^[5]. Hyaluronidase (12U/mL) treats MM6 cells, directly targeting HA and eliminating the HA signal^[6].

In vivo, hyaluronidase treatment of lymphedema model mice rapidly reduced the size of the edema area and enhanced lymphangiogenesis in the edematous limbs ^[7].

References:
[1] Menzel E J, Farr C. Hyaluronidase and its substrate hyaluronan: biochemistry, biological activities and therapeutic uses[J]. Cancer letters, 1998, 131(1): 3-11.
[2] Tao L, Song F, Xu N, et al. New insights into the action of bacterial chondroitinase AC I and hyaluronidase on hyaluronic acid[J]. Carbohydrate polymers, 2017, 158: 85-92.
[3] Weber G C, Buhren B A, Schrumpf H, et al. Clinical applications of hyaluronidase[J]. Therapeutic Enzymes: Function and Clinical Implications, 2019: 255-277.
[4] Vartanian A J, Frankel A S, Rubin M G. Injected hyaluronidase reduces restylane-mediated cutaneous augmentation[J]. Archives of Facial Plastic Surgery, 2005.
[5] Konopka A, Zeug A, Skupien A, et al. Cleavage of hyaluronan and CD44 adhesion molecule regulate astrocyte morphology via Rac1 signalling[J]. PloS one, 2016, 11(5): e0155053.
[6] Zahreddine H A, Culjkovic-Kraljacic B, Emond A, et al. The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity[J]. Elife, 2017, 6: e29830.
[7] Roh K, Cho S, Park J, et al. Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model[J]. Experimental Biology and Medicine, 2017, 242(6): 584-592.